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Ichio Aoki¹, Misao Yoneyama¹, Jun Hirose², Yuzuru Minemoto³, Takayoshi Koyama³, Sadahito Aoshima⁴, Jeff Kershaw¹, Kenji Kono², Yukihito Ishizaka³, Iwao Kanno¹

¹National Institute of Radiological Sciences, Chiba, Japan; ²Osaka Prefecture University, Osaka, Japan; ³International Medical Center of Japan, Tokyo, Japan; ⁴Osaka University, Osaka, Japan

A liposomal drug-delivery-system (DDS) will be help to avoid the side effects of chemotherapy by releasing anticancer drug at the tumor site. To improve the liposomal-DDS, we developed a multimodal thermo-sensitive polymer-modified liposomes (MTPL) and added new factors, long-term stability of the liposome in-vivo, passive accumulation in the tumor, and multimodal observation with MRI and optical imaging. The purpose of this study was to investigate whether 1) MRI and optical imaging can visualize MTPL accumulation in the tumor, 2) MTPL allows visualization of the drug-release after being triggered by mild-heating, and 3) MTPL can provide anti-tumor effects after treatment.

Ellen Ackerstaff¹, Khushali Kotedia¹, Mihai Coman¹, Kristen L. Zakian¹, Sean A. Burke¹, Sean D. Carlin¹, Joseph O'Donoghue¹, Clifton C. Ling¹, Jason A. Koutcher¹

¹Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Tumor hypoxia may influence treatment response and outcome. Thus, we investigated the potential of Trifluoromisonidazole (TFMISO) to measure hypoxia in solid tumors by in vivo ¹⁹F MRS and MRSI in two animal models of cancer breathing either air or 100% oxygen. Intratumoral TFMISO concentration increased with tumor growth in the MCa tumor model irrespective of amount of oxygen applied. In the R3327-AT model, intratumoral TFMISO levels were only moderately influenced by tumor growth but seemed to decrease in response to breathing of 100% oxygen in tumors below ~600mm³. Our results suggest that TFMISO may be useful for tumor hypoxia imaging by MR.

Beata Chertok¹, Allan E. David¹, Bradford A. Moffat², Brian D. Ross¹, Victor C. Yang¹

¹University of Michigan, Ann Arbor, Michigan, USA; ²University of Melbourne, Melbourne, Australia

This study investigated the utility of MRI to guide the alignment of a brain tumor lesion with magnetic field gradient to improve on specificity of magnetic nanoparticle accumulation within the tumor by an externally applied magnetic field in orthotopic 9L glioma model.

Anne H. Schmieder¹, Patrick M. Winter¹, Todd A. Williams¹, John S. Allen¹, Grace Hu¹, Huiying Zhang¹, Shelton D. Caruthers¹, ², Samuel A. Wickline¹, Gregory M. Lanza¹

¹Washington University School of Medicine, St Louis, Missouri, USA; ²Philips Medical Systems, Andover, Massachusetts, USA

Noninvasive high-resolution MR molecular imaging can provide a unique tool to characterize and quantify neovasculature in tumors. 3D neovascular mapping in mice implanted with MDA435 tumors revealed sparse neovascularity, which was further decreased with α5β1-targeted but not αvβ3-targeted antiangiogenic treatment. However, MDA435 tumor size was unaffected by either regimen, suggesting that MDA435 xenograft tumor growth has little dependence on angiogenesis, unlike previous results in the rabbit Vx2 model. These data illustrate the prognostic opportunities afforded by noninvasive high-resolution MR molecular imaging that may be clinically relevant in establishing personalized therapy regimens.

Deepak K. Kadayakkara¹, Lisa K. Pusateri¹, Hongyan Xu¹, Jelena M. Janjic¹, Eric T. Ahrens¹, ²

¹Carnegie Mellon University, Pittsburgh, Pennsylvania, USA; ²Pittsburgh NMR Centre for Biomedical Sciences, Pittsburgh, Pennsylvania, USA

In vivo oximetry of tumor tissues by MRI has enormous potential for preclinical evaluation of new therapeutics. Existing ¹⁹F relaxometry methods measure the pO₂ of the tumor cells indirectly from the sequestered perfluorocarbon nanoparticles in the tumor periphery following systemic administration.  In this study, we demonstrate the feasibility of measuring the direct intracellular pO₂ of 9L gliosarcoma cells in the rat brain using ¹⁹F MRS. The 9L glioma cells were labeled with perfluoro-15-crown-5 ether (CE) prior to implantation and pO₂ was measured using ¹⁹F T1 relaxation. The method will be used to study the real-time dynamics of tumor cell metabolism before and after the delivery of therapeutics.

Silvio Aime¹, Daniela Delli Castelli¹, Enzo Terreno¹, Claudia Cabella², Massimo Visigalli, Linda Chabaane, Stefania Lanzardo, Carla Carrera

¹University of Turin, Turin, Italy; ²CRM Cracco Imaging S.p.A., Italy

Dy(III) loaded liposomes are T2* susceptibility agents that provide an excellent visualization of tumors. The lack of specific tumor uptake in vivo has been associated to the efficient removal of liposomes operated by tumor associated macrophages.

Emily Alexandria Waters¹, Ralph W. Fuhrhop¹, John S. Allen¹, Gregory M. Lanza¹, Samuel A. Wickline¹

¹Washington University School of Medicine, Saint Louis, Missouri, USA

Once diagnosed, aortic valve disease can progress rapidly to critical stenosis requiring surgical valve replacement.  We illustrate the use of molecularly targeted drug-bearing nanoparticles for both early diagnosis and therapy of experimental aortic stenosis (AS) by targeting the inflammatory angiogenic components of AS with the use of αv β 3-integrin binding perfluorocarbon nanoparticles.  In this case MR spectroscopy of the unique 19F signal from the nanoparticles is used to quantify the extent of angiogenesis, which expresses the α;v β 3 integrin, and  to measure the response to antiangiogenic drug therapy.  We utilize a cholesterol-fed rabbit model of  AS that exhibits gross thickening, macrophage infiltration, and angiogenesis with abundant α;v β 3 endothelial biomarkers that can be quantified with 19F MRS to report drug efficacy.

Albert Yongwon Jin¹, Ursula I. Tuor², Jaspreet Kaur¹, Dave Rushforth², S Boutry³, Tadeusz Foniok², Robert N. Muller³, Boguslaw Tomanek², Philip A. Barber¹

¹University of Calgary, Calgary, Canada; ²National Research Council of Canada, Calgary, Canada; ³University of Mons-Hainaut, Mons-Hainaut, Belgium

Endothelial activation following cerebral ischemia and reperfusion involves the expression of the adhesion molecules P- and E-selectin. In a model of transient focal cerebral ischemia and reperfusion, magnetic resonance molecular imaging using the selectin-specific contrast agent Gd-DTPA-B(sLeX)A demonstrated differences in the accumulation of targeted and non-targeted contrast within the ischemic hemisphere in P-selectin knockout mice compared to the wild-type. These differences were correlated to the quantitative determination of P- and E-selectin expression in the brain, and led to the novel observation that E-selectin is upregulated in the ischemic hemisphere following acute stroke in P-selectin-deficient mice.

Mayumi Yamada¹, Paul T. Gurney¹, Pratima Kundu¹, Robert C. Robbins¹, Phillip C. Yang¹

¹Stanford University, Stanford, California , USA

Human embryonic stem cells (hESC) have demonstrated the ability to restore the injured myocardium. MRI has emerged as one of the predominant imaging modalities using iron-oxide nanoparticles to localize the transplanted cells in the myocardium. However, fundamental biological information regarding the viability of the transplanted cells can not be monitored. In this study, we employed MnCl2 (manganese chloride) guided cellular MRI to determine viability of hESC.

Monique Regine Bernsen¹, Amber Davinia Moelker¹, Sandra T. van Tiel¹, Gavin C. Houston², Gabriel P. Krestin¹, Piotr A. Wielopolski¹

¹Erasmus MC, Rotterdam, Netherlands; ²GE Healthcare, Den Bosch, Netherlands

The ability to track transplanted cells in vivo is considered a crucial point in the development and validation of cell-based therapy. To overcome some limitations of the negative contrast provided by labeling of cells with iron-oxide particles, we have developed an efficient labeling method for incorporation of Gd into cells. Using cationic lipid-based nano-particles (Gd-lipo) efficient labeling of stem cells was achieved allowing visualization of cells by positive contrast at single cell level. Also in vivo imaging of approximately 10.000 labeled cells injected in the myocardium of living syngenic cells was achieved.