Traditional Posters : Molecular Imaging
Click on to view the abstract pdf and click on to view the pdf of the poster viewable in the poster hall.
Targeted Molecular Imaging

 
Monday May 9th
Exhibition Hall  14:00 - 16:00

1651.   Brain tumor angiogenesis can be imaged by 19F MRI: high sensitivity detection of targeted PFOB emulsion in U87 human glioblastoma mouse model  
Céline Giraudeau1, Françoise Geffroy1, Aline Perrin1, Boucif Djemaï1, Benoît Thézé2, Philippe Robert3, Marc Port3, Caroline Robic3, Denis Le Bihan1, Franck Lethimonnier1, and Julien Valette1
1NeuroSpin, Commissariat à l'Energie Atomique, Gif sur Yvette, France, 2SHFJ, Commissariat à l'Energie Atomique, Orsay, France, 3Guerbet, Research Division, Roissy Charles de Gaulle, France

 
19F MRI has the unique property to specifically detect administered 19F-containing compounds without background signal and thus could be a substitute to PET imaging. Using a PFOB-dedicated, high sensitivity multi spin echo sequence, we show that 19F MRI is able to reveal brain tumors after injection of an RGD-functionalized PFOB emulsion targeting ávâ3 integrins. Our results are corroborated by fluorescence microscopy. This work demonstrates that 19F MRI may be an alternative to existing techniques to detect brain tumor angiogenesis.

 
1652.   Targeted iron oxide probes for enhanced macrophage visualization by MRI and PET 
Thomas S.C. Ng1,2, Chuqiao Tu3, Hargun Sohi1, Heather Palko3, Adrian House3, Russell E Jacobs1, and Angelique Y Louie3
1Beckman Institute, California Institute of Technology, Pasadena, CA, United States, 2Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, 3Biomedical Engineering, University of California, Davis, Davis, CA, United States

 
Rupture of atherosclerotic plaque leads to major events such as stroke and myocardial infarction. Thus, the imaging of vulnerable plaque is of great clinical interest. We have developed a method to coat iron oxide nanoparticles with sulfated dextran (SDIO), which demonstrate enhanced plaque macrophage uptake. We evaluated the in-vitro and in-vivo functionality of the SDIO compared to dextran coated IO. For clinical application, it is desirable to quickly target the particle signal with a highly sensitive marker before localized MRI. To pursue this concept, 64Cu-DOTA-SDIO was synthesized and used for PET/MR imaging in a mouse model of carotid plaque formation.

 
1653.   Molecular MRI of neurovascular inflammation in a mouse stroke model using bimodal ICAM-1 targeted nanoparticles 
Lisette Helene Deddens1, Geralda A Van Tilborg1, Annette Van der Toorn1, Leonie E Paulis2, Gustav J Strijkers2, Klaas Nicolay2, Gert Storm3, Willem J Mulder4, Helga E De Vries5, and Rick M Dijkhuizen1
1Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, 2Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 3Biopharmacy and Pharmaceutical Techonology, Utrecht University, Utrecht, Netherlands, 4Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, United States, 5Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands

 
Neuroinflammation is significantly involved in stroke pathophsiology, but underlying processes are still largely unraveled. Specific multimodal imaging probes may help to elucidate the pattern and contribution of distinct neuroinflammatory events, which eventually could make way for new or improved anti-inflammatory treatment strategies. We developed a liposomal contrast agent with paramagnetic and fluorescent lipids, targeted at intercellular adhesion molecule 1 (ICAM-1), which is upregulated on inflamed cerebrovascular endothelium and a potential marker of (sub)acute neuroinflammation. Our preliminary data demonstrate that anti-ICAM1-liposomes specifically bind to inflamed vasculature 24-48h after stroke in mice, which can be detected with MRI and fluorescent microscopy.

 
1654.   Ultra-short Echo Time 19F/1H Imaging of Gadolinium-free Perfluoro-carbon Nanoparticles: A Robust Method for In Vivo Angiogenesis Imaging 
Jochen Keupp1, Anne H Schmieder2, Todd A Williams2, J S Allen2, Samuel A Wickline2, Gregory M Lanza2, and Shelton D Caruthers2
1Philips Research Europe, Hamburg, Germany, 2C-TRAIN, Washington University School of Medicine, St. Louis, United States

 
Molecular imaging of integrin-targeted theranostic nanoparticles (NP) may offer profound impact on anti-angiogenic therapy. Previously, the value of lower case Greek alphalower case Greek nulower case Greek beta3-targeted nanoparticles (NP) with large payloads of Gd has been shown. This work presents a novel 19F pulse sequence to image clinically-relevant perfluoro-octyl-bromide (PFOB) NP without Gd. Using 19F/1H radial 3D balanced UTE-SSFP sequence, angiogenesis is imaged in a rabbit Vx2 cancer model comparing lower case Greek alphalower case Greek nulower case Greek beta3-targeted PFOB-NP with and without Gd. The new sequence is shown to allow robust, sensitive in vivo visualization of cancer-related neovasculature despite the complex resonant peak structure and the extended T1-relaxation time of Gd-free NP.

 
1655.   Dual-targeting of αvβ3–integrin and galectin-1 improves the specificity of paramagnetic, fluorescent liposome association with tumor endothelium in vivo 
Ewelina Kluza1, Igor Jacobs1, Stefanie J Hectors1, Kevin H Mayo2, Arjan W Griffioen3, Gustav J Strijkers1, and Klaas Nicolay1
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 2Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United States, 3Angiogenesis Laboratory, Department of Medical Oncology, VU Medical Center, Amsterdam, Netherlands

 
Recently, we showed that paramagnetic liposomes, which are concurrently targeted to two cell surface markers give a strong enhancement in endothelial cell association in vitro. Here, we tested the hypothesis that dual-targeted liposomes also afford a more specific tumor endothelial association in vivo, using C57BL/6 mice bearing s.c. B16F10 tumors. Paramagnetic liposomes targeted to αvβ3-integrin and galectin-1 at the same time were compared to single-marker targeted versions. Tumor delivery was monitored with T1W-MRI and T1 mapping. Fluorescence microscopy confirmed that the dual-targeted liposomes afforded the highest targeting specificity, making this an attractive concept for improved MRI-based tumor angiogenesis imaging.

 
1656.   Combined in vivo confocal laser scanning microscopy and magnetic resonance imaging to study an lower case Greek alphavlower case Greek beta3-integrin targeted nanoemulsion 
Sjoerd Hak1, Marte Thuen1, Peter A Jarzyna2, Willem J.M. Mulder2, Tore Syversen3, Catharina De Lange Davies4, and Olav Haraldseth1
1Department of Circulation and Medical Imaging, NTNU, Trondheim, Norway, Norway, 2Translational and molecular imaging institute, Mount Sinai School of Medicine, New York, New York, United States, 3Department of Neuroscience, NTNU, Trondheim, Norway, Norway, 4Department of Physics, NTNU, Trondheim, Norway, Norway

 
The application of nanoparticle molecular imaging probes is still primarily preclinical. The signal attenuation after i.v. injection of such agents is very variable throughout groups of subjects with the same pathological condition. This study aims to understand the underlying mechanisms for this variable enhancement patterns post-injection of an alpha-v-beta-3-integrin targeted nanoemulsion in tumors grown in an MRI compatible dorsal window chamber in mice. This experimental set-up represents a powerful tool as it allows studying dynamics and sub-cellular distribution of the targeted agents with in vivo confocal microscopy and correlating their effects with the clinically relevant MRI signal attenuation.

 
1657.   lower case Greek alphavlower case Greek beta3 -targeted nanoemulsions for tumor angiogenesis phenotyping with MRI and NIRF imaging 
Peter Adalbert Jarzyna1, Lisette Helene Deddens2, Benjamin H Kann1, Sarayu Ramachandran1, Claudia Calcagno1, Wei Chen1, Anita Gianella1, Rick M Dijkhuizen2, Arjan W Griffioen3, Zahi Adel Fayad1, and Willem JM Mulder1
1Translational and Molecular Imaging Institute, Radiology, Mount Sinai School of Medicine, New York, NY, United States, 2Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, 3Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, Netherlands

 
We developed an angiogenesis specific nanoemulsion platform for the noninvasive assessment of tumor angiogenesis and phenotyping with MRI and optical imaging. This agent was applied to two different nude mice tumor models with established differences in microvessel density (MVD) and angiogenic activity. We demonstrate in this study that after i.v. administration of our nanoparticles we could clearly distinguish the two tumor phenotypes. Differences in tumor biodistribution were shown by MRI, while differences in time resolved tumor accumulation were quantitatively assessed with near infrared fluorescence imaging.

 
1658.   Molecular MR Imaging of Liver Fibrosis with a Collagen-Targeting Gadolinium-Based Contrast Agent 
Miloslav Polasek1, Daniel T. Schühle1, Bryan C. Fuchs2, Jamu K. Alford1, Ronald J. H. Borra1, Kenneth K. Tanabe2, and Peter Caravan1
1Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, United States, 2Surgical Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States

 
Liver fibrosis occurs in advanced stages of chronic liver diseases, and proper staging of fibrosis is essential for prognosis, surveillance, and treatment decisions. Fibrosis is characterized by excess deposition of type I collagen in the parenchyma. We used a mouse model of liver fibrosis and imaged fibrotic and control animals before and after administration of a type I collagen-targeted Gd-based contrast agent. Increased signal enhancement and slower liver washout rates were imaging biomarkers that significantly distinguished mice with moderate fibrosis (Ishak grade 3-4) from age matched controls (Ishak grade 0).

 
1659.   Multi-Functional Imaging Agents for Site-Specific Detection of Prostate Cancer 
Quan-Yu Cai1,2, Huifang Zhai1, Prasanta nanda1,2, Charles Smith1,2, and Lixin Ma1,2
1Radiology, University of Missouri, Columbia, Missouri, United States, 2Harry S. Truman Memorial Veterans’ Hospital, Columbia, Missouri, United States

 
Prostate cancer is the second leading cause of cancer death among American men. Development of novel and non-toxic site-specific imaging agents will improve clinical outcomes in diagnosis and treatment of prostate cancer patients. In this project, we aim to synthesize and characterize magnetofluorescent nanoparticals for imaging prostate cancer. [AF750-BBN(7-14)]n-SPIO nanoparticles were synthesized and characterized for its binding affinity and specificity to gastrin releasing peptide receptor using a human prostate cancer PC-3 cell line and a severely compromised immunodeficient mouse model bearing PC-3 tumors. Our results suggest that [AF750-BBN(7-14)]n-SPIO nanoparticles will be useful for site-specific detection of prostate cancer.

 
1660.   In vivo molecular MRI of ICAM-1 expression in murine cardiac ischemia/reperfusion using a liposomal nanoparticle 
Leonie E Paulis1, Igor Jacobs1, Nynke M van den Akker2, Bram F Coolen1, Tessa Geelen1, Klaas Nicolay1, and Gustav J Strijkers1
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 2Department of Cardiology, University of Maastricht, Maastricht, Netherlands

 
In vivo molecular MRI of ICAM-1 expression on vascular endothelium after ischemia/reperfusion induced myocardial infarction was explored using ICAM-1 targeted paramagnetic liposomes. The contrast agent formulation was optimized to enhance ICAM-1 specific association. Using this formulation, MRI could distinguish low from high levels of cellular ICAM-1 expression in vitro. In addition, under physiological shear stress conditions, ICAM-1 specific binding was observed. In vivo circulation kinetics and biodistribution were determined with MRI and confocal microscopy. In vivo cardiac T1w MRI showed signal enhancement in infarcted myocardium using ICAM-targeted liposomes compared to control lipsomes, which was confirmed by ex vivo microscopy.

 
1661.   Targeted MnFe2O4-Erbitux-CyTE777 nanoparticles toward high EGFR expressing cancer cells for in vitro and in vivo MR imaging 
Gin-Chung Liu1,2, Yun-Ming Wang3, Ming-Hong Chen3, Kun-Liang Lin3, and Chiao-Yun Chen1,4
1Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, 2Department of Radiology, Kaohsiung Medical University, Kaohsiung, Taiwan, 3Biological Science and Technology, National Chiao Tung University, Hsin Chu, Taiwan, 4Department of Radiology, Kaohsiung Medical University, Taiwan

 
Technological limitations of imaging modality often hold back diagnosis and therapy of cancer. It is widely accepted that early diagnosis may lead to cure or at least offer extended life to the cancer patient. Recent studies have demonstrated that Erbitux can be potentially employed for targeted drug delivery to tumor site. Herein, we report EGFR specific multimodal imaging agents, MnFe¬¬2O4-Erubitux-CyTE777 nanoparticles. MR imaging studies were performed with a 3.0 T MR imager and body fluorescent images were carried out by IVIS spectrum imaging system. Thus, the multimodal nanoparticles could be potentially used as contrast agents for molecular MR imaging.

 
1662.   A peptide-targeted MRI contrast agent for cancer molecular imaging 
Xueming Wu1, Mingqian Tan1, and Zheng-Rong Lu1
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

 
This study designed, synthesized and evaluated a peptide-based low molecular weight MRI contrast agent specific to a cancer-related biomarker for cancer molecular imaging with MRI. The cancer imaging effectiveness of the targeted agent was demonstrated by using athymic nude mice bearing orthotopic human prostate PC-3 tumor model. Our preliminary results showed the agent was able to deliver a sufficient amount of Gd-DOTA chelates to its molecular target. The newly developed targeted agent is promising for cancer MR molecular imaging.

 
1663.   The binding of CNA-35 conjugated nanoparticles to assembled versus disassembled collagen fibrils 
Honorius M.H.F. Sanders1,2, M Iafisco3, E M Pouget2, P H.H. Bomans2, F Nudelman2, G Fallini3, G de With2, Maarten Merkx4, N A.J.M. Sommerdijk2, Gustav J Strijkers1, and Klaas Nicolay1
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 2Laboratory of Materials and Interface Chemistry, Department of Chemistry, Eindhoven University of Technology, Eindhoven, Netherlands, 3Università del Piemonte Orientale, Novara, Italy, 4Biomedical Chemistry, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

 
Collagen imaging can contribute to improved diagnosis and therapy of various diseases. Recently, CNA-35 conjugated paramagnetic micelles and liposomes were introduced as collagen-specific MRI contrast agents. Here we tested the hypothesis that these nanoparticles primarily bind to single collagen triple helices rather than mature collagen fibrils, and thus could provide unique tools for MR imaging of disease processes that involve active collagen remodeling. With the use of cryo-TEM, we indeed demonstrate that CNA-35 bearing liposomes and micelles selectively bind to poorly assembled collagen, whereas the monomeric CNA-35 protein also binds to ordered collagen fibrils.

 
1664.   Multifunctional Nanoparticles Incorporating a Gadolinium Labelled Peptide for Therapuetic Delivery and Switchable MR Contrast Monitoring of Delivery 
Gavin D Kenny1,2, Katharina Welser3, Frederick Campbell3, Aristides D Tagalakis1, Helen C Hailes3, Alethea B Tabor4, Mark F Lythgoe2, and Stephen L Hart1
1Molecular Immunology Unit ICH, University College London, London, United Kingdom, 2UCL Centre for Advanced Biomedical Imaging, Division of Medicine and Institute of Child Health, University College London, London, United Kingdom, 3Department of Chemistry, University College London, London, United Kingdom, 4Department of Chemistry, UCL, London, United Kingdom

 
Nanoparticles that not only mediate functional delivery of therapeutic payload, but also allow monitoring of delivery by MRI are of great interest. Here we describe liposome nanoparticles incorporating a Gd labelled peptide, that act as 'switchable' MR contrast agents, in that upon delivery of the DNA payload inside the cell the signal is enhanced.

 
1665.   VEGFR2 expression in C6 and RG2 glioma models using molecular MRI 
Ting He1, Nataliya Smith1, Debra Saunders1, Robert Silasi-Mansat2, Florea Lupu2, Megan Lerner3, and Rheal Towner1
1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States, 2Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States, 3Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States

 
Angiogenesis is essential to tumor progression and the precise imaging of angiogenic marker of Vascular endothelial growth factor receptor 2 (VEGFR2) would provide accurate evaluation for angiogenesis. This study is to characterize varied angiogenesis status in C6 and RG2 glioma models by assessing expression of VEGFR2 using molecular magnetic resonance imaging (MRI) with an anti-VEGFR2-albumin-Gadolinium (Gd)-DTPA-biotin probe. The results showed that VEGFR2 expressed heterogeneously in different regions in C6 gliomas, whereas was more relatively homogenous in RG2 gliomas. In conclusion, the expression pattern of VEGFR2 using molecular MRI can be used as an accurate marker to evaluate active tumor-associated angiogenesis.

 
1666.   Magnetic resonance imaging of c-fos gene transcription after burn trauma using a superior contrast agent 
Valeria Righi1,2, Aristarchos Papagiannaros1,2, Jianxin He3, George Dai2, Laurence Rahme3, Vitaliano Tugnoli4, Philip K Liu2, Ronald G. Tompkins5, Bruce R Rosen2, and Aria A. Tzika1,2
1Department of Surgery, NMR Surgical Laboratory, MGH and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States, 2Department of Radiology, Athinoula A. Martinos Center of Biomedical Imaging, Boston, MA, United States, 3Department of Surgery, Molecular Surgery Laboratory, MGH and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States,4Departement of Biochemistry, University of Bologna, Bologna, Bologna, Italy, 5Department of Surgery, MGH and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States

 
Our aim was to produce a superior contrast agent that will be administered using systemic as opposed to local administration, which will target and accumulate to the burn site. Specifically, we developed and delivered pegylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparticles (USPION) coated with polymer modified fusogenic lipids and covalently linked to a phosphorothioate-modified oligodeoxynucleotide complementary to c-fos mRNA and imaged mice subjected leg burn. Our study demonstrates the feasibility to monitor burn injury using MR imaging of c-fos transcription in vivo, in a clinically relevant mouse model of burn trauma for the first time.

Traditional Posters : Molecular Imaging
Click on to view the abstract pdf and click on to view the pdf of the poster viewable in the poster hall.
Novel Contrast Agents & Labels

 
Tuesday May 10th
Exhibition Hall  13:30 - 15:30

1667.   Reduced glutathione rather than oxygen concentration determines the reduction rate of nitroimizadol probes used as hypoxia markers. 
Jesus Pacheco-Torres1,2, Paloma Ballesteros2, Pilar Lopez-Larrubia1, and Sebastian Cerdan1
1Biomedical Research Institute "Alberto Sols" - CSIC/UAM, Madrid, Spain, 2Laboratory of Organic Synthesis and Molecular Imaging, UNED, Madrid, Spain

 
Nitroimidazolyl derivatives (Pimonidazole, Misonidazole, EF5) have been traditionally used by different imaging methods as markers for hypoxia due to their preferential reduction and subsequent trapping in vivo under hypoxic conditions. However, these results remained difficult to interpret since the reduction mechanism and its rate determining steps remained largely unexplored. We address here the latter two aspects. We show that it is the intracellular redox state (NADP/NADPH, GSSG/GSH), rather than the oxygen tension, what determines the reduction rate of these compounds, the rection rate being limited mainly by the GSH concentration. This is a general mechanism occurring in all nitromidazolyl derivatives investigated.

 
1668.   In vivo magnetic resonance imaging of Eu3+-based PARACEST contrast agents using SWIFT 
Todd C. Soesbe1, Osamu Togao1, Masaya Takahashi1, and A. Dean Sherry1,2
1Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Department of Chemistry, The University of Texas at Dallas, Dallas, TX, United States

 
Paramagnetic chemical exchange saturation transfer (PARACEST) agents use water molecule exchange with lanthanide ions and radiofrequency (RF) spin saturation to create negative contrast in MRI. One advantage that PARACEST agents have over Gd-based T1 agents is that image contrast can be turned off and on via the RF saturation pulse frequency. We have recently shown that chemical exchange of water molecules between Eu3+-based PARACEST agents and bulk water can also facilitate T2 exchange (T2exch). T2exch causes a significant reduction in the bulk water T2 (i.e. negative contrast) for agents with high local concentrations, intermediate exchange rates, and large chemical shifts. The negative contrast is present even when the RF saturation pulse is omitted, causing the PARACEST agents to behave like susceptibility or T2 agents. We hypothesized that the ultra-short TE (<10 μs) used in the SWIFT sequence could reclaim the loss in signal due to T2exch and enable fast and sensitive in vivo PARECEST imaging.

 
1669.   Nano-size MR probe detects T cells infiltration in bone marrow and growth plate in rat model of rheumatoid arthritis 
Chih-Lung Chen1, Cheng-Hung Chou2, Ming-Huang Lin2, Wen-Yuan Hsieh1, Hsin-Hsin Shen1, Shian-Jy Wang1, and C. Chang2
1Industrial Technology Research Institute, Hsinchu, 310, Taiwan, 2Academic Sinica, Taiwan

 
The activation of T-cells correlates with the pathogenesis of rheumatoid arthritis (RA). Understanding the genesis, migration, and distribution of the T-cells provides important perspectives regarding RA. To monitor T-cells noninvasively and repeatedly, an in vivo labeling technique using a new nanoparticle contrast agent, IOPC, was employed. The IOPC had a longer blood circulation time that allowed uptake by cells over a longer duration. Noticeable IOPC-induced hypointensities was observed in the growth plate of the RA rat one day following in vivo IOPC labeling. Double immunohistology against IOPC and CD3 confirmed the presence of T-cells in the growth plate in RA.

 
1670.   R2 enhancement by formation of a tungsten-iron alloy crystal in the apoferritin cavity 
Veronica Clavijo Jordan1, and Kevin M Bennett1
1School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States

 
Nanoparticles have been developed as T2 contrast agents for molecular MRI. However, there is still a need to develop agents with higher relaxivities in order to increase sensitivity to delivered agents in vivo. In this work, we formed a tungsten-iron alloy in the interior cavitiy of apoferritin. The use of the protein to form a crystal core enhances the magnetic properties of the particle. The yield of the process when compared to magnetoferritin was enhanced by 200%. The W-Magnetoferritin nanoparticles had a per-iron and per-particle transverse relaxivity of 27,666mM-1s-1and 433,651mM-1s-1 respectively, which is a ~10% increase over magnetoferritin nanoparticles.

 
1671.   Dual MRI-SPECT agent for pH-mapping 
Eliana Gianolio1, Luca Maciocco2, Daniela Imperio3, Giovanni Battista Giovenzana3, Federica Simonelli4, Kamel Abbas4, Gianni Bisi5, and Silvio Aime1
1Dept. Chemistry IFM & Molecular Imaging Center, University of Torino, Torino, Italy, Italy, 2Advanced Accelerator Applications (AAA), St. Genis Pouilly, France, 3DiSCAFF, University of Eastern Piedmont “A. Avogadro", Novara, Italy, 4European Commission Cyclotron, Institute for Health and Consumer Protection Joint Research Centre, Ispra (VA), Italy, 5, Nucl Med Serv, Azienda Osped San Giovanni Battista, Dipartimento Med Interna, University of Torino, Torino, Italy

 
In vitro study of a dual MRI/SPECT pH-responsive agent where the SPECT-active moiety (based on a Ho(III) containing complex) acts as a reporter of the concentration of the MRI active one (based on a Gd(III) containing complex) thus allowing the transformation of the observed 1H-relaxation rates into relaxivities to recover the information relative to the pH determination.

 
1672.   Imaging hypoxia using a nitroimidazole based T1 MR contrast agent 
Praveen Kumar Gulaka1, Federico A Rojas-Quijano2, Zoltan Kovacs2, Ralph P Mason1,3, A D Sherry2,3, and Vikram D Kodibagkar1,3
1Joint graduate program in Biomedical Engineering, UT Arlington and UT Southwestern Medical Center, Dallas, Tx, United States, 2Advanced Imaging Research Center, UT Southwestern Medical Center, 3Radiology, UT Southwestern Medical Center

 
Hypoxic regions in tumors are known to affect radiation sensitivity and promote development of metastases. Therefore the ability to image the tumor hypoxia in vivo will provide useful prognostic information and help tailor therapy. Previous research demonstrated that 2-nitroimidazole accumulated in hypoxic tissues due to an enzyme mediated reduction of the nitro group in hypoxic conditions. In this work, we report both in vitro and in vivo evidence for accumulation of a T1 shortening agent, a GdDOTA monoamide conjugate of 2-nitroimidazole abbreviated as GdDO3NI, in hypoxic tumor tissue.

 
1673.   Measuring in vivo tumor pHe with a PARACEST MRI contrast agent 
Vipul R Sheth1, Yuguo Li2, Liu Qi Chen3, Christine A Howison4, and Mark D Pagel5
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, 2Radiology, Case Western Reserve University, Cleveland, OH, United States, 3Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States, 4Arizona Research Laboratories, University of Arizona, Tucson, AZ, United States, 5Biomedical Engineering and Chemistry & Biochemistry, University of Arizona, Tucson, AZ, United States

 
A PARACEST MRI contrast agent, Yb-DO3A-oAA, can measure pH over a range of 6-7.9 pH units, with a precision of 0.206 pH units and an accuracy of 0.089 pH units. This measurement is based on a ratio of the two CEST effects of the PARACEST agent, which is independent of the agent's concentration or the samples T1sat relaxation time. Combined with a CEST-FISP acquisition protocol, the PARACEST agent was used to measure the extracellular pH (pHe) within a subcutaneous tumor and muscle of a MDA-MB-231 breast cancer model.

 
1674.   Targeted Magnetoliposomes for visualization of Hepatocytes 
Ashwini A Ketkar-Atre1, Stefaan J. Soenen2, Philip Roelandt3, Tineke Notelaers3, Greetje Vande Velde1, Catherine Verfaillie3, Marcel De Cuyper4, and Uwe Himmelreich1
1Biomedical NMR Unit/MoSAIC, KULeuven Campus Gasthuisberg, Leuven, Flanders, Belgium, 2Department of Pharmaceutical Sciences, Ghent University, Belgium, 3Interdepartmental Stem Cell Institute, KULeuven Campus Gasthuisberg, 4Lab of BioNanoColloids, KULeuven Campus Kortrijk, IRC, Belgium

 
In diseases like liver cirrhosis or hepatitis where hepatocytes are damaged and healing is difficult, it is necessary to isolate hepatocytes from mixed population of endo- and mesodermal cells differentiated from stem cells. We labelled HepG2s, C17.2 (negative control) and mixture of cells containing hepatocytes like cells with Cationic MLs (unspecific uptake), Anionic MLs (negative control) and Lac MLs with galactose-terminal entities which are recognized by asialoglycoprotein receptors (ASGPR). Higher specificity in uptake was observed with Lac MLs labelling with hepatocytes. And In vivo experiments revealed the potential use of Lac MLs as a contrast agent for liver therapy evaluation.

 
1675.   A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity 
Yuguo Li1, Vipul R Sheth2, Guanshu Liu3,4, and Mark D Pagel5
1Radiology, Case Western Reserve University, Cleveland, OH, United States, 2Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, 3Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 4F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 5Biomedical Engineering and Chemistry & Biochemistry, University of Arizona, Tucson, AZ, United States

 
We have developed a new esterase-responsive PARACEST MRI contrast agent. Before esterase cleavage, the agent Yb-DO3A-oAA-TML-ester has only one CEST signal at -11 ppm from an amide proton. Esterase de-esterification forms an amine in the product Yb-DO3A-oAA, which creates a second PARACEST signal at +9 ppm. The two CEST effects of the product endows self-calibration with respect to pharmacokinetic factors such as the concentration of agent and resulting possible shortening of T1sat relaxation time, providing a more accurate way to detect esterase enzyme activity without needing a reference agent.

 
1676.   Magnetic resonance imaging of organic contrast agents: applications to redox imaging and radioprotection 
Ryan Miller Davis1, Shingo Matsumoto1, Marcelino Bernardo2,3, Anastasia Sowers1, Ken-Ichiro Matsumoto4, Murali C Krishna1, and James B Mitchell1
1Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland, United States, 2Molecular Imaging Program, National Cancer Institute, Bethesda, Maryland, United States, 3National Cancer Institute-Frederick, Frederick, Maryland, United States, 4National Institute of Radiological Sciences, Molecular Imaging Center, Chiba, Japan

 
Nitroxides are a diverse class of organic small molecular weight (170-400 Da) paramagnetic radioprotectors. Because nitroxides are paramagnetic, their pharmacodynamics can be monitored indirectly with MRI. This study uses a 3 Tesla human scanner to measure pharmacodynamics of various nitroxides after tail vein injection in mice. In addition, radioprotection studies of those nitroxides were carried out with 300kVp x-rays in a dose range of 6-12.5 Gy. The results of this study provide invaluable information regarding possible causes of nitroxide toxicity, the relationship between nitroxide pharmacokinetics and radioprotective potency, and healthy tissue and tumor redox status.

 
1677.   Release Activated Iron Oxide Nanoparticles (REACTION) of Cellulose: A Magnetic Relaxation Switch for Environmentally sensitive MRI 
Michael K Nkansah1, and Erik M Shapiro1,2
1Department of Biomedical Engineering, Yale University, New Haven, CT, United States, 2Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States

 
While magnetic relaxation switches (MRSws) have been developed using iron-oxide particles that cluster in the presence of an extracellular stimulus, the potential of using such systems to monitor intracellular events in vivo via MRI has not been investigated. Granot et al first demonstrated an MRSw operating in cellulo and in vivo via MRI using a Feridex®/dextranase system. We demonstrate the fabrication of magnetic cellulose particles that are relaxometrically sensitive to cellulase digestion. In the ‘off’ state, the particle remains intact. When switched ‘on’ through the cleavage action of cellulase, the iron-oxide cores get dispersed, changing the relaxivity of the agent.

 
1678.   Graphene- Based MRI Contrast Agents: Synthesis, Characterization and In vitro MRI 
Bhavna S Paratala1, Lindsay K Hill2, Lilliane Mujica-Parodi1, Elisabeth de Castro Caparelli3,4, Youssef Zaim Wadghiri2, and Balaji Sitharaman1
1Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States, 2Department of Radiology, New York University Langone Medical Center, New York, New York, United States, 3Medical Department, Brookhaven National Laboratory, Upton, New York, United States, 4Social, Cognitive and Affective Neuroscience Center, Stony Brook University, Stony Brook, New York, United States

 
We report the synthesis, characterization (structure, magnetism and relaxometry) and in vitro MRI of graphene oxide nanoribbon (GONR)-based MRI contrast agents (CAs) for cellular and molecular MRI. GONRs were synthesized by chemical “unzipping” of multiwalled carbon nanotubes using the oxidizing agent potassium permanganate. HRTEM and Raman spectroscopy confirm the presence of GONRs. Magnetic (SQUID), and NMR relaxatometry studies reveal room temperature superparamagnetism, and relaxivities of r1 = 45mM-1s-1 and r2 = 234mM-1s-1, respectively. T1-, T2- weighted MRI phantom images show significant contrast enhancement compared to Manganese chloride, widely used preclinical CA .

 
1679.   Mechanical release from paramagnetic liposomes triggered by low frequency ultrasound 
Enzo Terreno1, Pierangela Giustetto1, Daniela Delli Castelli1, Cinzia Boffa1, Davide Durando1, and Silvio Aime1
1Molecular and Preclinical Imaging Center, University of Torino, Torino, Italy

 
The mechanical (i.e. non-thermic) release of the liposomal content (MRI agent and/or drug) by using pulsed low-frequency low-intense ultrasound is strongly affected by small changes in the bilayer composition, payload of imaging probe (or drug), size and shape of the nanovesicles. This finding offers the opportunity to selectively trigger the release of imaging reporters, as well as drugs, from a mixture of different nanocarriers, thus opening new therapeutic schemes to improve the overall efficacy of a pharmacological treatment.

 
1680.   Gd-complex of Macrocyclic DTPA Conjugate of 2,2prime or minute-Diaminobiphenyl: A New MR Contrast Agent for Both Angiography and Brain-Tumor Imaging 
Ki-Hye Jung1, Hee-Kyung Kim2, Min-Kyoung Kang2, Ji-Ae Park3, Seung-Tae Woo4, Joo-Hyun Kim4, Tae-Jeong Kim1, and Yongmin Chang2,5
1Department of Applied Chemistry, Kyungpook National University, Daegu, Korea, Republic of, 2Department of Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, Republic of, 3Laboratory of Nuclear Medicine Research, Molecular Imaging Center, Korea Institute of Radiological & Medical Science, Seoul, Korea, Republic of, 4Bayer Schering Pharma Korea, Seoul, Korea, Republic of, 5Department of Diagnostic Radiology and Molecular Medicine, Kyungpook National University, Daegu, Korea, Republic of

 
We report the synthesis of Gd-complex of macrocyclic DTPA conjugate of 2,2¡¯-diaminobiphenyl (GdL) for use as a new MR contrast agent for both angiography and brain-tumor imaging. GdL exhibits very high R1 relaxivity (= 12.15 mM-1sec-1) which is 3.3 times as high as that of structurally related macrocyclic analogue, Dotarem® R1(= 3.7 mM-1sec-1). Also observed is the greater kinetic stability than those of commercially available Omniscan® and Multihance®. The present system shows a very strong blood-pool effect for as long as 2 h, and most uniquely demonstrates brain-tumor imaging capability which is absent from the ordinary ECF MRI CAs.

 
1681.   Gd-complexes of DOTA conjugates of tranexamates: A new class of non-aromatic, non-ionic MRI blood-pool contrast agents 
Hee-Kyung Kim1, Ki-Hye Jung2, Min-Kyoung Kang1, Ji-Ae Park3, Seung-Tae Woo4, Joo-Hyun Kim4, Tae-Jeong Kim2, and Yongmin Chang1,5
1Department of Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, Republic of, 2Department of Applied Chemistry, Kyungpook National University, Daegu, Korea, Republic of, 3Laboratory of Nuclear Medicine Research, Molecular Imaging Center, Korea Institute of Radiological & Medical Science, Seoul, Korea, Republic of, 4Bayer Schering Pharma Korea, Seoul, Korea, Republic of, 5Department of Diagnostic Radiology and Molecular Medicine, Kyungpook National University, Daegu, Korea, Republic of

 
Gd-complexes of the type [Gd(L)(H2O)]·H2O(5a-c), where L is DOTA conjugates of tranexamic acid (4a)and tranexamic esters (4b-c), have been prepared as a new class of MRI BPCAs. Thermodynamic stability (KGdL) and pharmacokinetic inertness of 5 are compared well with or better than those of analogous MRI CAs such as Gd-DOTA and Gd-DTPA-BMA. Their R1-relaxivities are significantly higher than any of the clinically used MRI CAs. T1-weighted MR images of mice administered by 5c demonstrate high blood-pool effect with simultaneous contrast enhancement in liver.

 
1682.   Gadolinium oxide for molecular and cellular MRI: A cautionary tale 
Simone S Williams1,2, Tricia L Lobo3, and Erik M Shapiro1,3
1Department of Biomedical Engineering, Yale University, New Haven, CT, United States, 2Xavier University of Louisiana, New Orleans, LA, United States, 3Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States

 
We investigated the use of gadolinium oxide (Gd2O3) based contrast agents for MRI-based cell tracking. Gd2O3 nanocrystals were synthesized and encapsulated within PLGA to form 150 nm nanoparticles. While PLGA encapsulated Gd2O3 nanoparticles had good r1 molar relaxivity, 1.9 mM-1sec-1, Gd2O3 nanocrystals rapidly dissolved to form gadolinium ions in solutions mimicking lysosomal chemical environment within cells. Thus, while Gd2O3 does have favorable MRI properties, the rapid dissolution of Gd2O3 to form gadolinium ions is dangerous and needs to be accounted for when using Gd2O3 as an MRI contrast agent.

 
1683.   Alginate-Coated Magnetic Nanoparticles as a New Platform for Noninvasive Calcium MR Imaging In Vivo 
Debbie Anaby1, Liat Avram1, Amnon Bar-Shir2, Ofer Sadan3, Smadar Cohen4, Niva Segev-Amzaleg5, Dan Frenkel5, Daniel Offen3, and Yoram Cohen1
1School of Chemistry, Tel Aviv University, Tel Aviv, Israel, 2Johns Hopkins University, Baltimore, Maryland, United States, 3Department of neurology, Rabin Medical Center, Tel Aviv University, Tel Aviv, 4Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben Gurion University of the Negev, Beer Sheva, Israel, 5Department of Neurobiology, the Goerge Weiss Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

 
Calcium cations are involved in myriad of biological processes and pathologies. Despite the crucial role played by calcium in living systems, the noninvasive determination or imaging of calcium levels in opaque samples and deep tissues remains a formidable challenge. Here we describe a new platform based on superparamagnetic iron oxide nanoparticles coated with mono-disperse alginate, which enables specific detection of Calcium, by MRI. These nanoparticles were shown to detect calcium secreted in Quinolinic Acid lesions in rats brains in vivo. This new non-invasive MRI biomarker for calcium has the potential to act as a calcium probe in in vivo settings.

 
1684.   Measurement of the Singlet-State Lifetime of N2O in Rat Blood: Its Potential As An MRI Tracer 
Rajat K. Ghosh1, Stephen J. Kadlecek1, Kiarash Emami1, Benjamin M. Pullinger1, Giuseppe Pileio2, Malcolm H. Levitt2, Nicholas N. Kuzma1,3, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2School of Chemistry, Southampton University, Southampton, Hampshire, United Kingdom, 3Departments of Biomedical Engineering and Imaging Sciences, University of Rochester, Rochester, NY, United States

 
Development of hyperpolarized MRI tracers is often limited by the longitudinal relaxation rate due to dipolar interactions. It has been previously demonstrated that the effect of dipolar interactions in solution can be removed by storing the nuclear polarization of molecules in long-lived, singlet-like spin states. In the case of doubly-enriched 15N2O storing the polarization of 15N nuclei in the singlet state has been shown to substantially increase their polarization lifetime. The feasibility of utilizing 15N2O as a tracer is investigated by measuring the singlet lifetime of15N2O when dissolved in a variety of solvents including whole blood. Comparing the singlet lifetime to the T1 relaxation in deuterated and natural solvents sheds light on the mechanism of the singlet state relaxation

 
1685.   Extravasation of a New High Molecular Weight Contrast Agent in Tumour Vasculature, Probed by MRI & Histology 
Kelly Catherine McPhee1, Jennifer E.H. Baker1,2, Katayoun Saatchi3, Urs O Häfeli3, and Stefan A Reinsberg1
1Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada, 2Radiation Biology Unit, BC Cancer Research Centre, Vancouver, British Columbia, Canada,3Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada

 
In this pilot study, we investigate a novel, high-molecular weight (HMW) contrast agent, hyperbranched polyglycerol (HPG), doubly labeled with Gd and a fluorescent marker. Longitudinal measures of T1 were made in vivo. We observed accumulation of HPG over several days, followed by a drop after about a week both in MRI (via changes in T1 baseline), and in histology (via the fluorescent tag). Histology shows HPG remains within or proximal to vasculature at early time points, but extravasates and accumulates at greater distances from vessels over time.
1686.   Isostructural Re and 99mTc Complexes of Gd-DTPA-Histidine for Dual-Modality MR/SPECT imaging agents 
Ji-Ae Park1, Jung Young Kim1, Byoung Soo Kim1, Wonho Lee1, In Ok Ko1, Joo Hyun Kang1, Sang Moo Lim2, Hee-Kyung Kim3, Yongmin Chang3, Tae-Jeong Kim4, and Kyeong Min Kim1
1Molecular Imaging Research Center, Korea Institute of Radiological & Medical Science, Seoul, Nowon-Gu, Korea, Republic of, 2Department of nuclear Medicine, Korea Institute of Radiological & Medical Science, 3Department of Medical & Biological Engineering, Kyungpook National University, 4Department of Applied Chemistry, Kyungpook National University, Korea, Republic of

 
The combination of magnetic resonance imaging (MRI) and nuclear medicine imaging can be representative synergistic approach for providing anatomical and functional information together, because of the high resolution of MRI and the high detector sensitivity of radionuclide imaging, respectively. In this study, we report the Gd-DTPA-histidine conjugated of 99mTc complexes [GdLHis_99mTc] as MR/SPECT dual modality contrast agents. To overcome problems in hybrid imaging due to the huge difference (~103) of imaging sensitivity between MRI and SPECT, we suggest the mixed-usage of [GdLHis_99mTc] with Gd-DTPA-histidine conjugated of Re complexes [GdLHis_Re] that is an alternative substance(cold-form) having chemical characteristics equivalent with [GdLHis_99mTc]. A new hybrid 99mTc labeled MR contrast could be made and be suitable to both MRI and SPECT imaging. The identical characteristics of [GdLHis_99mTc] and [GdLHis_Re] showed the same bio-functional change of hybrid contrast agents, with the additional merit of improved MRI image quality. Therefore, the hybrid-usage of both [GdLHis_Re] and [GdLHis_99mTc] should be useful in the optimal acquisition of MR/SPECT imaging that is prerequisite for precise interpretation of bio-function.

 
1687.   Heteroditopic binding of MR contrast agents for increased relaxivity 
Zhaoda Zhang1, Matthew Greenfield2, Andrew Kolodziej2, and Peter Caravan1
1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States, 2Epix Pharmaceuticals, Lexington, MA, United States

 
Fibrin-specific peptides conjugated to multiple Gd-chelates, e.g. EP-2104R and EP-1242, have shown efficacy in MR detection of thrombus. We hypothesized that a second small binding group at the N-terminus may provide additional fibrin affinity, while at the same time would restrict internal motion at the N-terminus upon fibrin binding and this would result in higher relaxivity. We demonstrate that a minor perturbation (addition of a thymine moiety at the N-terminus) in probe structure can result in a 50% increase in relaxivity at the target, but does not increase off-target relaxivity. This heteroditopic binding approach is generalizable to other protein-targeted probes.

 
1688.   A new R2/R1 Ratiometric Method to Measure pH with a Dendrimer-based pH-Responsive MRI Contrast Agent 
Meser M. Ali1, Parvez Ismail Bhuiyan1, Hassan Bagher-Ebadian2,3, Branislava Janic1, Robert A knight2,3, James R. Ewing2,3, and Ali Syed Arbab1
1Radiology, Henry Ford Hospital, Detroit, MI, United States, 2Neurology, Henry Ford Hospital, 3Physics, Oakland University

 
We have recently developed a new pH-responsive dendrimer-based MRI contrast agent with excellent improvements in both overall sensitivity and responsiveness of relaxivities to pH. Therefore, the R2/R1 ratio of this dendritic MR agent has been used to measure pH and the ratio (r2/r1) showed pH-response. This pH measurement is independent of the absolute concentration of the agent so that a single MRI agent can measure pH without requiring a second MRI to account for pharmacokinetics.

 
1689.   New biodegradable multimeric MPIO contrast agent shows rapid in vitro and in vivo degradation and high sensitivity contrast 
Francisco Perez-Balderas1,2, Benjamin G Davis2, Sander I vanKasteren2, Alexandr Khrapichev1, Andrew Jefferson3, Claire Bristow1, Sebastien Serres1, Robin P Choudhury3, Daniel C Anthony4, and Nicola R Sibson1
1CR/UK Gray Institute for Radiation Oncology & Biology, University of Oxford, Oxford, Oxfordshire, United Kingdom, 2Chemistry Research Laboratory, University of Oxford, Oxford, Oxfordshire, United Kingdom, 3Department of Cardiovascular Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom, 4Department of Pharmacology, University of Oxford, Oxford, Oxfordshire, United Kingdom

 
Superparamagnetic iron oxide (SPIO) nanoparticles have been extensively used for several biomedical applications. Recently, microparticles of iron oxide (MPIO) have been advantageously employed in cellular tracking and early detection of endovascular pathologies. Unfortunately, the commercially available MPIO used suffer from a lack of biodegradability that precludes their medical use. We have developed fully biodegradable multimeric MPIO (mMPIO) with a size ca. 1 lower case Greek mum that combine the superior imaging capabilities of MPIO with the excellent biodegradability and clearance of SPIO. We demonstrate here both in vitro and in vivo degradation of our novel mMPIO, and their sensitive in vivo contrast effects.

 
1690.   Synthesis and Evaluation of PARACEST MRI Contrast Agents Containing an Amino Acid Arginine 
Mojmir Suchy1,2, Alex X. Li2, Mark Milne1, Robert Bartha2, and Robert H. E. Hudson1
1Chemistry, University of Western Ontario, London, Ontario, Canada, 2Robarts Research Institute, University of Western Ontario, London, Ontario, Canada

 
A new synthetic methodology for the preparation of Tm3+-derived PARACEST MRI contrast agents containing an amino acid arginine has been developed. The CEST sensitivity of these molecules has been evaluated and found to be comparable to that of Tm3+ DOTAM-Gly-Lys-OH, a PARACEST MRI contrast agent previously detected in mouse kidneys and mouse brain tumours.

 
1691.   A Novel Gadolinium-Based Contrast Agent Targeted to Cathepsin-D 
Robert Ta1,2, Alex X Li1, Mojmir Suchy3, Robert H.E Hudson3, Stephen Pasternak4,5, and Robert Bartha1,2
1Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada, 2Medical Biophysics, The University of Western Ontario, London, Ontario, Canada, 3Chemistry, The University of Western Ontario, London, Ontario, Canada, 4Molecular Brain Research Group, Robarts Research Institute, London, Ontario, Canada, 5Clinical Neurological Sciences, The University of Western Ontario, London, Ontario, Canada

 
A novel contrast agent, Gd3+-DOTA-CAT, has been developed for in-vivo magnetic resonance imaging of Cathepsin-D activity in Alzheimer’s disease. A cell-penetrating-peptide was attached to increase the agent’s ability to cross the blood-brain-barrier. A Cathepsin-D recognition site was used for enzymatic detection of Gd3+-DOTA-CAT upon brain tissue penetration. We compared the MR sensitivity of Gd3+-DOTA-CAT to Gd3+-DTPA(Magnevist®) to evaluate the potential in-vivo imaging of this compound. Injection of 10 mM Gd3+-DOTA-CAT in a transgenic Alzheimer’s disease mouse produced increased signal intensity within the brain, cerebral and non-cerebral vasculature. Gd3+-DOTA-CAT demonstrates significant potential as a MRI contrast agent for Cathepsin-D activity in-vivo.

 
1692.   Gd-Albumin Relaxivity in the Rat Thalamus In Vivo at 11.1 T 
Garrett William Astary1, Svetlana Kantorovich2, Paul Richard Carney1,3, Malisa Sarntinoranont4, and Thomas Harold Mareci5
1Biomedical Engineering, University of Florida, Gainesville, FL, United States, 2Neuroscience, University of Florida, 3Division of Pediatric Neurology, University of Florida, 4Mechanical and Aerospace Engineering, University of Florida, 5Biochemistry and Molecular Biology, University of Florida

 
A priori knowledge of contrast agent (CA) relaxivity (R1 and R2), which parameterizes how a CA alters neighboring water proton relaxation times (T1 and T2), can be used to determine the CA concentration in tissue, using pre- and post-contrast T1-weighted scans and knowledge of inherent tissue T1 values. The relaxivity of the CA gadolinium-labeled albumin (Gd-albumin) was measured in rat thalamus in vivo at 11.1 T and compared to the relaxivity of this CA measured in solution. R1 and R2 values in tissue were found to be reduced by 78% and 32%, respectively relative to solution values.

 
1693.   Efficacy of different lipid-coated nanoclusters of iron oxide for image-based detection of labeled cells 
Geralda A.F. van Tilborg1, David P. Cormode2, Peter A. Jarzyna2, Annette van der Toorn1, Susanne M.A. van der Pol3, Louis van Bloois4, Gert Storm4, Willem J.M. Mulder2, Helga E. de Vries3, and Rick M. Dijkhuizen1
1Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, 2Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, United States, 33Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands, 4Department of Pharmaceutics, Institute for Pharmaceutical Sciences, Utrecht, Netherlands

 
MRI-based in vivo cell tracking studies require potent and biocompatible contrast agents with high labeling efficiency, and, preferentially, inclusion of fluorescent entities for additional microscopic analyses. In the present study we compared three different types of fluorescent lipid-coated nanoclusters of iron oxide, with or without inclusion of an oil phase. Nanoparticles without oil showed superior properties in terms of relaxivity r2, shelf-life, labeling efficiency of murine macrophages and biocompatibility. In conclusion, lipid-coated nanoclusters of iron oxide represent an attractive, potent and flexible platform with, in the absence of an oil phase, excellent properties for cellular imaging.

 
1694.   Copper Nanoparticles for T1-Weighted MR Molecular Imaging 
Shelton D. Caruthers1, Dipanjan Pan1, Angana Senpan1, Anne H. Schmieder1, Patrick J. Gaffney2, Samuel A Wickline1, and Gregory M Lanza1
1C-TRAIN, Washington University School of Medicine, St. Louis, MO, United States, 2Dept. of Surgery, St. Thomas' Hospital, London, United Kingdom

 
Based on a nanocolloidal suspension of lipid-encapsulated, organically-soluble copper oleate, a new site-targeted molecular imaging contrast agent is presented. Concentrating ~100,000 copper atoms per nanoparticle, this agent provides a high per-particle r1 relaxivity allowing sensitive detection on T1-weighted MRI as is demonstrated herein targeted to fibrin clots in vitro.

 
1695.   Multi-Modality PET-MR Perfluorocarbon Nanoparticle Contrast Agent for Ligand-Targeted Quantitative Imaging 
Shelton D. Caruthers1, Monica Shokeen2, Ricardo Ferdani2, Hua Pan1, Samuel A Wickline1, and Carolyn J. Anderson2
1C-TRAIN, Washington University School of Medicine, St. Louis, MO, United States, 2Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States

 
The combination of PET and MRI is a major step in the evolution of molecular imaging. This work introduces a novel multi-modality contrast agent detected by both PET and MRI. Based on a lipid-encapuslated liquid perfluorocarbon nanoparticle platform, the agent uses a self-inserting chelator with a linker peptide derived from melittin to allow straightforward labeling with 64Cu. Quantitative MR imaging results from direct detection of the 19F signal from the nanoparticle core.

 
1696.   A new biodegradable MR contrast agent with high kinetic chelation stability for cancer imaging 
Zhen Ye1,2, Xueming Wu2, Mingqian Tan2, and Zheng-Rong Lu2
1Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, United States, 2Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States

 
This study designed, synthesized and evaluated a novel biodegradable polymeric MRI contrast agent with high kinetic stability for clinical cancer diagnosis using contrast-enhanced MRI. The new agent showed high relaxivity and good degradability in vitro. The MR contrast-enhancing effect of the new agent was evaluated on mice bearing orthotopic 4T1 breast cancer tumor. Our in vivo preliminary results demonstrated the agent was able to generate significantly prolonged and higher tumor enhancement than clinical agents. The novel contrast agent is of great clinical potential for MR cancer diagnosis.

 
1697.   Magnetoliposomes open up new horizons as MRI contrast agents. 
Stefaan Soenen J.H. Soenen1, Michel Hodenius1, Marcel De Cuyper1, and Uwe Himmelreich2
1Lab of BioNanoColloids, IRC, Katholieke Universiteit Leuven Campus Kortrijk, Kortrijk, Belgium, 2Biomedical NMR Unit/ MoSAIC, Katholieke Universiteit Leuven, Leuven, Flandern, Belgium

 
Magnetoliposomes (ML) have been developped and studied) for stable, non-toxic, longitudinal cell labelling and monitoring. In contrast to other iron oxide based nanoparticles, MLs are stable intracellularly for a long time, don't cause adverse effects on cell biology and result in stronger T2* contrast. The later is due to gradual, intracellular degredation of the outer lipid layer and subsequent clustering of the monolayer-coated iron oxide particles.

 
1698.   Detection of in vivo Enzyme Activity with PARACEST MRI 
Byunghee Yoo1, Vipul R Sheth2, Christine A Howison3, Matthew Douglas4, Carlos T Pineda5, Amanda F Baker6, and Mark D Pagel7
1Biomedical Engineering, University of Arizona, Tucson, AZ, United States, 2Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, 3Arizona Research Laboratories, University of Arizona, Tucson, AZ, United States, 4College of Medicine, University of Arizona, Tucson, AZ, United States, 5Arizona Cancer Center, University of Arizona, Tucson, AZ, United States, 6Hematology/Oncology, Arizona Cancer Center, University of Arizona, Tucson, AZ, United States, 7Biomedical Engineering and Chemistry & Biochemistry, University of Arizona, Tucson, AZ, United States

 
We have detected the enzyme activity of urokinase Plasminogen Activator within a Capan-2 pancreatic tumor model. After i.v. injection of a mixture of a uPA-responsive PARACEST agent and an unresponsive "control" PARACEST agent, CEST-FISP MR images were acquired for 18 minutes to monitor both agents. The initial increase in CEST effects in the tumor from both agents was equivalent indicating equivalent pharmacokinetics, but the CEST effect of the enzyme-responsive agent decreased more rapidly than the CEST effect of the control agent after 6 minutes, indicating that the agent was being cleaved by uPA.

 
1699.   Development of an activatable MRI T2 agent sensitive to NADH 
Elizabeth A Osborne1, and Angelique Y Louie2
1Chemistry, University of California, Davis, Davis, CA, United States, 2Biomedical Engineering, University of California, Davis, Davis, CA, United States

 
We have developed MRI contrast agents based on paramagnetic nanoparticles functionalized with “molecular switches”, that are capable of reporting on redox conditions. The “molecular switches”, spirooxazine, change conformation between hydrophilic and hydrophobic isomers in response to NADH and peroxide. This isomerization directs aggregation and dispersion of the nanoparticles yielding a modulation of MR signal. We have synthesized and characterized iron oxide nanoparticles coated with dextran that has been cross-linked and aminated thus allowing attachment of spirooxazine. Preliminary results indicate successful preparation of the particles, and size and relaxivity differences have been observed upon reaction with NADH/peroxide in solution studies.

 
1700.   measurement of T1,T2 relaxation time as assembly conditions of gold nanoparticles 
Dong-Hyuk Kim1, Yong-Hee Han1, Moo-Young Jang1, and Chi -Woong Mun1,2
1Biomedical Engineering, Inje University, KimHae, KyeongNam, Korea, Republic of, 2UHRC

 
This study, typical MR variables such as T1-and T2-relaxation times of the tissue-mimic phantoms which include the lab-made gold nanoparticles(GNP) were measured according to their morphological characteristics and synthesis conditions.

Traditional Posters : Molecular Imaging
Click on to view the abstract pdf and click on to view the pdf of the poster viewable in the poster hall.
Cell Tracking & Gene Reporters

 
Wednesday May 11th
Exhibition Hall  13:30 - 15:30

1701.   Imaging of DIACEST Microcapsules containing Hepatocytes using Length Variation of Saturation and Principal Component Analysis 
Xiaolei Song1,2, Kannie W.Y. Chan1,2, Guanshu Liu1,3, Dian A. Arifin1,2, Assaf A. Gilad1,2, Peter C.M. Van Zijl1,3, Jeff W.M. Bulte1,2, and Mike T. McMahon1,3
1Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, 2Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United States, 3F.M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States

 
We have developed a new method to acquire and process CEST images in regions with field inhomogeneities and motion. Images are acquired with varying the saturation pulse length at only one saturation offset(+∆ù). Principle component analysis (PCA) is then used to produce contrast maps. The resulting maps have higher CNR values and less artifacts than those produced using saturation offset incrementation, and the scan time is reduced by at least half. To test this method, we transplanted DIACEST microcapsules into the abdomen of mice, and monitored the contrast using both the proposed method and conventional method acquiring multiple frequency offsets.

 
1702.   Longitudinal evaluation of MPIO-labeled stem cell biodistribution in a GBM model using MR imaging and DCE-MRI at 14.1Tesla 
Myriam Marianne Chaumeil1, Christopher G Boyd2, Beatrice Gini3, Raquel Santos2, Jacqueline de la Torre2, Christina Ng2, Huijan Yang3, Akio Iwanami3, Subramanian Sukumar1, Tomoko Ozawa2, Russel O Pieper2, Paul Mischel3, C David James2, and Sabrina M Ronen1
1Radiology, University of California, San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California San Francisco, San Francisco, CA, United States, 3Pathology & Lab. Medicine, University of California Los Angeles, Los Angeles, CA, United States

 
In an effort to design an efficient stem cell (SCs)-based therapy product for the treatment of glioblastoma (GBM) tumors, we compared the pathotropism of two different SCs sources towards GBM tumors, human mesenchymal stem cells (hMSCs) and fetal neural stem cells (fNSCs). Using MR imaging and dynamic contrast enhanced MRI at 14.1Tesla, MPIO-labeled hMSCs and fNSCs biodistributions were characterized over a 7-day period. The tropism of both fNSCs and hMSCs was found to be comparable: both SCs types first localized at the tumor edges, in highly neovascularized regions, then in the tumor mass and also further away tracking tumor microsatellites.

 
1703.   High sensitivity 19F MRI allows dynamic biodistribution study and oxygen tension mapping at pharmaceutical doses of a PFOB emulsion in the mouse reticuloendothelial system 
Céline Giraudeau1, Boucif Djemaï1, Sidi Mohamed Ould Ahmed Ghaly1, Philippe Robert2, Marc Port2, Caroline Robic2, Denis Le Bihan1, Franck Lethimonnier1, and Julien Valette1
1NeuroSpin, Commissariat à l'Energie Atomique, Gif sur Yvette, France, 2Guerbet, Research Division, Roissy Charles de Gaulle, France

 
PFOB emulsions are promising tracers for quantitative 19F MRI of the reticuloendothelial system (RES). Using a PFOB-dedicated multi spin echo (MSE) sequence, we show that kinetics of accumulation of PFOB nanoparticles in the RES can be quantified and that stealth of emulsions including different quantities of polyethylene glycol can be assessed. Moreover, oxygen pressure mapping can be performed in the RES after one single injection of emulsion. These results are promising for monitoring of the RES status in vivo.

 
1704.   In vivo MRI-Based Cell Tracking Using Bio-MPIOs 
Michael K Nkansah1, Dorit Granot2, Tricia L Lobo2, and Erik M Shapiro2
1Department of Biomedical Engineering, Yale University, New Haven, CT, United States, 2Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States

 
Bio-MPIOs are biodegradable micron sized iron oxide particles fabricated using an FDA approved polymer. Here we describe design improvements to PLGA encapsulated iron oxide nano- and microparticles, experiments on magnetic cell labeling, cell differentiation and cytokine release experiments, and ultimately, the first in vivo demonstration of MRI-based cell tracking using PLGA encapsulated iron oxide microparticles, or, Bio-MPIOs. This is the first demonstration of MRI-based cell tracking using Bio-MPIOs and is encouraging for the development of these particles for clinical MRI-based cell tracking.

 
1705.   Bimodal labelling of S. aureus for detection of bacterial colonization in skin infections by MRI 
Verena Hoerr1, Lorena Tuchscherr2, Bettina Loeffler2, Lydia Wachsmuth1, Klaus Strobel1, Florian Schmid1, and Cornelius Faber1
1Department for Clinical Radiology, University Hospital Muenster, Muenster, Germany, 2Institute of Medical Microbiology, University Hospital Muenster, Muenster, Germany

 
We have developed a protocol for labelling S. aureus with rhodamine coated iron-oxide particles (VSOPs). In mouse models of S. aureus infection we were able to visualize bacterial colonies in tissue and to distinguish infection from inflammation both by MRI and Fluorescence Reflectance Imaging (FRI). Using ultra-short echo-time imaging (UTE) and FLASH with complementary image contrast iron particles in bacterial colonization were detected and confirmed by fluorescence imaging. To the best of our knowledge we present the first MRI visualization of S. aureus colonization in mouse models in vivo.

 
1706.   3D Ultra Short TE MRI for Whole Subject Imaging of Perfluorocarbon-Labeled Cell Biodistribution 
T Kevin Hitchens1,2, Qing Ye1, and Chien Ho1,2
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States, 2Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States

 
We applied a 3D ultra-short TE (UTE3D) sequence to image the biodistribution of in vivo perfluorocarbon (VS-1000) labeled immune cells using a hetertopic heart and lung transplantation model in rats. Following direct i.v injection, a 19F-UTE3D can detect VS-1000 in circulation and at 24 hrs, shows the distribution of labeled cells in the rat. The UTE3D is an efficient technique for 3D imaging and less sensitive motion artifacts than traditional phase encoding of k-space. This technique can be generally applied and the simplicity of animal preparation, and independence of pilot scans is favorable for increased throughput and screening.

 
1707.   Cellular MRI for Mapping Proliferation During Tumour Development 
Lisa Michelle Gazdzinski1, and Brian J Nieman1
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada

 
Although tumours are comprised of a diverse population of cells, evaluation of tumour progression and treatment response most often consists of simple volume measurements, which cannot account for the heterogeneity in the cell population or in the corresponding tumour growth. We show that iron oxide labelling of tumour cells can be used to spatially map proliferative activity within a developing mouse glioma tumour. These methods represent a new role for cellular imaging techniques in cancer research and provide a platform for more detailed preclinical evaluation of novel cancer therapies.

 
1708.   Verification of metabolite peak change during chondrogenesis of human mesenchymal stem cells using Proton NMR 
Moo-Young Jang1, So-Hee Park1, Jung-woog Shin1,2, and Chi-Woong Mun1,2
1Biomedical Engineering, Inje University, Gimhae, Gyeongnam, Korea, Republic of, 2UHRC, Inje University, Gimhae, Gyeongnam, Korea, Republic of

 
This paper is intended to investigate on metabolite changes of chondrogenic hMSCs using 1H NMR to confirm the differentiation. Chondrogenic hMSCs were resuspended to 0.9% saline D2O and was filled in 5mm NMR tube (2x106cells/500¥ìl). We confirmed differentiation by alcian blue staining. NMR spectrum data were acquired using 500MHz NMR spectrometer with the following parameters: PRESAT sequence, relaxation delay=20ms, 45¡Æ pulse, NT=512. We confirmed that peak intensities of 1H MR spectrum tend to increase at 1.33/1.48/1.49/2.94-2.97/3.23/3.56/ 3.78 ppm after the onset of chondrogenic differentiation from hMSCs. On the other hand, lipid and fatty acid peaks were reduced during the differentiation.

 
1709.   Intra-cellular Sodium Concentration and Intra-cellular Volume Fraction Quantification in the Human Brain using 7T MRI in-vivo. 
Lazar Fleysher1, Niels Oesingmann2, Ryan Brown1, Hina Jaggi1, Graham Wiggins1, Daniel Sodickson1, and Matilde Inglese1,3
1Radiology, NYU School of Medicine, New York, New York, United States, 2Siemens Medical Solutions USA, Malvern, PA, United States, 3Neurology, NYU School of Medicine, New York, New York, United States

 
A majority of sodium MRIs performed to date provide a global measure of the tissue sodium content, while the most useful information about tissue viability is contained in the intracellular compartment. Here, we show that the intracellular sodium concentration (ISC) and the intracellular sodium volume fraction (ISVF) can be obtained from the tissue sodium concentration (TSC) and the intracellular sodium molar fraction (ISMF) using MRI. The developed method has high potential for clinical and research applications since it allows non-invasive quantitative mapping of the ISMF, ISVF and ISC in-vivo and may be used to study the function of healthy and diseased organs, to monitor disease progression, and to guide treatment.

 
1710.   Improving Detection of Micron Size Magnetic Particles Using Linear Phase Ramps 
Stephen J Dodd1, Gary Zabow1, James P Sumner1, and Alan P Koretsky1
1Laboratory of Functional and Molecular Imaging, NINDS, National Institutes of Health, Bethesda, MD, United States

 
The contrast from micron size magnetic particles is dependent on the position within a voxel under certain imaging conditions. It is shown that the contrast maybe adjusted and improved with application of linear phase ramps in k-space to give sub-voxel image shifts. This technique will provide improved quantification of particle distributions for cell tracking experiments.

 
1711.   Targeting mesenchymal stem cells (MSC) using pulsed focused ultrasound: Implications for stem cell therapy 
Ali Ziadloo1, Scott R. Burks1, Aneeka Chaudhry1, Eric M. Gold1, Dana D. Dean1, Bobbi K. Lewis1, Kay Jordan1, Victor Frenkel1, and Joseph A. Frank1
1Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD, United States

 
Stem cell therapy shows great potential to treat various diseases but can be limited by poor targeting to tissues. We demonstrate that pulsed focused ultrasound (pFUS) creates non-destructive mechanical effects which trigger expression of proinflammatory cytokines, and used pFUS in the kidney to enhance migration of mesenchymal stem cells (MSC). Mouse kidneys were treated with pFUS followed by superparamagnetic iron oxide nanoparticle (SPION)-labeled human MSCs. In vivo and ex vivo T2* MRI of the kidney revealed increased accumulation of MSCs to pFUS-treated kidneys versus control kidneys, and was confirmed by histological examination including immunohistochemisrty.

 
1712.   Non-invasive Evaluation of Chronic Cardiac Rejection after Heart Transplantation with Multi-parameter Cellular and Functional MRI 
Qing Ye1, Yijen L Wu1, Lesley M Foley1, Brent D Barbe1, Fang-Cheng Yeh1, T. Kevin Hitchens1, Li Liu1, and Chien Ho1
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States

 
Cardiac allograft chronic rejection (CR) remains a major obstacle for long-term graft survival after heart transplantation. Non-invasive assessment of cardiac allograft status is highly desirable. We are developing non-invasive means for detecting allograft rejection using cardiac MRI techniques. In this study, we used a heterotopic rat model of CR to investigate longitudinal characteristics of CR progression over time with multi-parameter cellular and functional MRI. Our preliminary results indicate that simultaneous cellular and tagging MRI can evaluate rejection status non-invasively over time, which may be a reliable alternative for assessment of CR and potentially translate to clinical arena.

 
1713.   Enhanced MRI visualization of endogenous neuroblasts migration by optimizing MPIO formulations 
Dorit Granot1, and Erik M Shapiro1,2
1Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States, 2Department of Biomedical Engineering, Yale University, New Haven, CT, United States

 
In vivo labeling of endogenous neuroblasts in brain is an established method for tracking native cell migration in vivo. MPIOs are injected into the lateral cerebral ventricle proximal to the neural stem cell niche and are endocytosed by neural progenitor cells, making them visible by T2* weighted MRI. However, the in vivo efficiency of MPIO uptake into stem and progenitor cells remains low. We have previously demonstrated that enhanced cell labeling can be achieved in culture using a mixture of MPIOs and transfection agent. Here we extend this method to enhance in vivo MRI detection of migrating precursor stem cells.

 
1714.   R2*-lower case Greek rho Imaging on Rat Allograft Cardiac Transplantation with Acute Rejection: A Preliminary Study 
Fang-Cheng Yeh1, Yijen L. Wu2, Qing Ye2, T. Kevin Hitchens2, and Chien Ho2
1Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States, 2Pittsburgh NMR Center for Biomedical Research, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA

 
A new imaging modality called R2*-£m imaging is proposed to detect ultra-small superparamagnetic iron oxide (USPIO) nanoparticle-labeled cells in rat cardiac tissue modeling acute allograft rejection. By introducing an additional spin density term, R2*-£m imaging is shown to provide a higher specificity than regular R2* image in term of their vunerabilibity to the suscupetibility artifact occurred in the air-tissue junctions. The resulting images demonstrate a clearer image background, with the existence of iron particles presented in high intensity, which offers a more specific identification of the rejection site. The specificity feature of R2*-£m Imaging may provide a better quantification analysis on the severity of the rejection.

 
1715.   Intralymphatic cancer cell tracking with two MRI contrast agents: SPIO / quantum dot cell labeling with Gd-dendrimer lymphangiography in the mouse model 
Nobuyuki Kosaka1, Marcelino Bernardo1, Makoto Mitsunaga1, Peter L. Choyke1, and Hisataka Kobayashi1
1Molecular Imaging Program, National Cancer Institute, Bethesda, MD, United States

 
We dual-labeled cancer cells with a quantum dot and SPIO, and tracked them within the lymphatic system with in vivo MRI and optical imaging. By employing a dendrimer-based T1-weighted MRI contrast agent, MR lymphangiography simultaneously depicted cancer cells and draining lymphatic basins around the injected sites. In vivo functional drainage of lymphatic basins and migration of cancer cells were visualized with a single MRI scan. Additionally, fluorescence imaging provided cancer cell tracking at higher spatial resolution than MRI. Thus, MR and optical imaging can be a powerful research tool for investigating lymphatic metastases.

 
1716.   In-vivo MRI of cell migration towards QA induced lesions in the mouse brain 
Prodromos Parasoglou1, Joe J Rodriguez1, Cesar A Berrios-Otero1, Brian J Nieman2, and Daniel H Turnbull1
1Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, United States, 2Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada

 
Multipotent neurobalsts (NBs) are produced throughout life by neural stem cells in the forebrain subventricular zone (SVZ) and can travel long distances to the olfactory bulb along the rostral migratory stream (RMS). On arrival in the bulb, NBs replace olfactory neurons suggesting their potential use for novel cell replacement therapies. In this study we report the use of MRI to follow simultaneously the movement of magnetically labeled SVZ cells along the RMS and towards a quinolinic acid (QA) lesion. The ability to directly monitor cell migration in the mouse brain will enable important investigations of neural cell response to injury.

 
1717.   Repetitive Imaging of Tumor Cell Growth Using Gene-based, Iron Contrast: MagA vs. Modified Ferritin Subunits 
Roja Rohani1, Rene Figueredo2, Jim Koropatnick2, Paula Foster3, R Terry Thompson1, Frank S Prato1, and Donna Elizabeth Goldhawk1
1Imaging, Lawson Health Research Institute, London, ON, Canada, 2London Regional Cancer Program, London, ON, Canada, 3Imaging, Robarts Research Institute, London, ON, Canada

 
We followed the appearance of endogenous contrast in iron-supplemented, tumor cells injected into immune-compromised mice. Repetitive MRI on anesthetized animals, from several days post-injection up to 5 weeks, compared MagA-expressing cell growth to that of modified ferritin subunits, lacking iron response elements, and parental controls. Nascent tumors were detected days after injection on a 3T scanner using a custom RF coil and gradient insert. This study documents the activity of an undifferentiated cancer cell line using noninvasive, live animal imaging to improve our understanding of cancer stem cell biology, cell transplantation, and the potential of reporter gene expression for MRI.

 
1718.   Modifying Polyethylene Glycol Effects Liposome Relaxivity and Enhances Tumour Cell Uptake for Drug Delivery 
Tammy Louise Kalber1,2, Nick J Mitchell3, Simon Walker-Samuel1, Quentin A Pankhurst4, Helen C Hailes3, Alethea B Tabor3, Sam M Janes2, and Mark F Lythgoe1
1Centre for Advanced Biomedical Imaging, Division of Medicine and Institute of Child Health, University College London, London, United Kingdom, 2Centre for Respiratory Research, Department of Medicine, University College London, University College London, London, United Kingdom, 3Department of Chemistry, University College London, London, United Kingdom, 4Davy-Faraday Research Laboratories, The Royal Institution of Great Britain, London, United Kingdom

 
Two formulations of bimodal liposomes, carrying both gadolinium chelates and fluorescent markers with different modifications of the polyethylene glycol (PEG) chain (named ME42 and CH300 liposomes), were used to assess how PEG can affect both liposomal relaxivity and cell uptake. Relaxivity measurements, as well as cell uptake analysis by reduction of T1 on MR images, and fluorescence by both fluorescence microscopy and flow cytometry. ME42 PEG liposomes demonstrated reduced relaxivity, and cellular uptake compared to CH300 PEG liposomes. This therefore indicates that altering PEG synthesis is essential for the optimization of liposomes as both contrast agents and drug delivery systems. microscopy and flow cytometry. ME42 PEG liposomes demonstrated reduced relaxivity, and cellular uptake compared to CH300 PEG liposomes. This therefore indicates that altering PEG synthesis is essential for the optimization of liposomes as both contrast agents and drug delivery systems.

 
1719.   Neuralized iPSCs can migrate to gliomas: MRI findings 
Tyler James McKay1, Samuel E Nutt2, Jiakai Li1, Norman J Beauchamp1, Xiaoming Yang1, Philip J Horner2, and Bensheng Qiu1
1Radiology, University of Washington, Seattle, WA, United States, 2Neurosurgery, University of Washington, Seattle, WA, United States

 
Induced pluripotent stem cells (iPSCs) offer tremendous potential to the field of regenerative medicine by providing an unlimited supply of patient-specific stem cells. Here we show that neutralized iPSCs (niPSC) are capable of migration to brain tumors with in vivo tracking by magnetic resonance imaging (MRI). SPIO-labeled niPSCs and T98G glioma cells were implanted at contralateral sites in the brains of five nude mice. Weekly MRI scans reveal selective migration of niPSCs across the brain to the tumor mass. This finding is an important preliminary step in developing iPSC technology into clinical cell therapies for human diseases.

 
1720.   The use of Cellular MRI to study the role of Cancer Stem Cells in metastasis development in vivo 
Emeline Julie Ribot1, Carmen Simedrea2, Ann F Chambers2, and Paula J Foster1
1Imaging Laboratories, Robarts Research Institute, London, Ontario, Canada, 2London Regional Cancer Program, London, Ontario, Canada

 
Problem: Patient survival decreases to 15.9% when melanoma has metastasized. Cellular MRI was used to monitor melanoma cell fate, to study the influence of cancer cell environment on proliferation and dormancy states. Methods: MPIO-labeled mouse melanoma cells were administered into mice by intracardiac injection or via the mesenteric vein. MRI was performed at 3T using a bSSFP sequence. Results: In the brain, many voids were initially detected, but their number decreased over time. No metastasis was observed. In the liver, metastasis developed while some cancer cells stayed dormant. Conclusion: This study highlighted the importance of cell environment in metastasis growth.

 
1721.   In vivo Implementation of REACTION (Release Activation of Iron Oxide Nanoparticles) 
Dorit Granot1, and Erik M Shapiro1,2
1Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States, 2Department of Biomedical Engineering, Yale University, New Haven, CT, United States

 
Here we describe a new enzyme/contrast agent paradigm which can achieve enzymatically responsive changes in cellular T2 and T2*. Cells are labeled with particles coated with a biopolymer that restricts the approach of water to the particle, preventing the magnetic core from relaxing protons. Cleavage of the coat by a specific enzyme reveals the magnetic center thus increasing the relaxivity of the agent. In an in vivo demonstration of this paradigm, large enhancements of dark contrast volume and CNR within the contrast regions were measured, for injected cells co-labeled with enzyme and particles versus cells labeled with particles alone.

 
1722.   Design of Thymidine Analogs as CEST Reporters for Imaging of HSV1-TK Expression 
Amnon Bar-Shir1,2, Guanshu Liu1,3, Michael T McMahon1,3, Martin G Pomper4, Peter C van Zijl1,3, Jeff W Bulte1,2, and Assaf A Gilad1,2
1Division of MR Research, the Russel H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4The Russel H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

 
Herpes simplex virus type-1 thymidine kinase (HSV1-TK) is an enzyme that phosphorylates a wide range of nucleoside analogs and has been used extensively for imaging gene expression using positron emission tomography (PET). Here we demonstrate for the first time that native nucleosides can generate specific MRI contrast based on the chemical exchange saturation transfer (CEST) mechanism. Furthermore, chemical modifications can improve their CEST-MRI fingerprints considerably. Specifically, the synthetic analog 5,6-dihydrothymidine (DHT) and thymidine triphosphate improved, by more than two-fold, the CEST-MRI contrast over thymidine. These results indicate that using these substrates, HSV1-TK can be used as CEST-MRI reporter.

 
1723.   The magnetosome membrane protein Mms6 produces MR contrast in vitro 
Xiaoyong Zhang1, Brenda Robledo1, Steven Harris1, and Xiaoping Hu1
1Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States

 
Magnetotactic bacteria produce organelles called magnetosomes that contain iron oxide crystals. Mms6 is a protein thought to initiate magnetite crystal nucleation within the magnetosome. Because of this function, we hypothesized that mms6 expressed in mammalian cells would function as a reporter gene by effecting iron oxide crystal formation that can be measured with MRI. We isolated a clonal cell line expressing mms6 and incubated the cells in iron supplemented growth media. We found a statistically significant increase in transverse relaxivity, R2, with increasing iron concentration for the cells expressing mms6 suggesting it may function as an MR reporter gene.

 
1724.   Monitoring tissue response to hyperbaric oxygen intervention using PISTOL 
Praveen Kumar Gulaka1, Edmond Richer2, and Vikram D Kodibagkar1,3
1Joint graduate program in Biomedical Engineering, UT Arlington and UT Southwestern Medical Center, Dallas, Tx, United States, 2Mechanical Engineering, Southern Methodist University,3Radiology, UT Southwestern Medical Center

 
The ability to quantitatively measure tissue oxygen tension (pO2) non-invasively could have a significant impact on understanding the mechanisms of tissue function and in clinical prognosis of cancer and peripheral vascular disease. Previously, PISTOL (Proton Imaging of Siloxanes to map Tissue Oxygenation Levels) was shown as an oximetry technique to quantitatively measure pO2. Here we demonstrate the use of hexamethyldisiloxane (HMDSO) based nanoemulsions for mapping muscle pO2 using PISTOL technique and determined a kinetic parameter (k) related to oxygen consumption, in response to normobaric and hyperbaric oxygen challenge.

 
1725.   Genetic Engineering of Human Protamine-1 for use as MRI Reporter Gene Based on Proton Exchange 
Amnon Bar-Shir1,2, Guanshu Liu1,3, Xiaolei Song1,2, Piotr Walczak1,2, Michael T McMahon1,3, Peter C van Zijl1,3, Jeff W Bulte1,2, and Assaf A Gilad1,2
1Division of MR Research, the Russel H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

 
Several strategies for MR imaging of gene expression have been developed, each with its own specific contrast mechanism to generate signal from reporter genes. Here, we demonstrate that human protamine-1 (hPRM1), an arginine-rich protein, generates superior MRI contrast based on the chemical exchange saturation transfer (CEST) mechanism. To this end, recombinant hPRM1 was engineered to be expressed in E. coli. The dialyzed bacterial lysate showed a much higher CEST contrast as compared to control proteins, suggesting that hPRM1 is a promising new CEST reporter gene.