13:30
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Direct & Indirect MRI Methods to Detect Drug Delivery 
Christin Y. Sander1,2
1A. A. Martinos Center for Biomedical
Imaging, Department of Radiology, Massachusetts General
Hospital, Charlestown, MA, United States, 2Harvard
Medical School, Boston, MA, United States
Drug properties are initially defined through in vitro
studies and characterized by parameters such as efficacy
and affinity. However, in vivo drug profiles can vary
widely and depend on the type of imaging modality used,
species, methods of administration, and what we define
as outcome measures. In this talk, we will show how we
can use PET as a direct and fMRI as an indirect method
to image drug delivery and its functional response.
Taken together, we can establish models that link drug
occupancy to functional output and classify drugs
according to their in vivo potency.
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13:50
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Theranostics: Delivering Drug & Contrast Agent
Simultaneously
Willem Mulder1
1MSSM, United States
In this educational imaging-facilitated optimization of
nanomedicine and the “companion diagnostic" concept, the
latest advances in these fields, and translational
considerations will be discussed.
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14:10
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Use of MRI to Monitor Drug Delivery in Combination with
Focused Ultrasound
Chrit T. Moonen1 and
Clemens Bos1
1UMC Utrecht
The recently published examples of the use of MR-HIFU
for local drug delivery illustrate the important role of
multi-modal molecular imaging in the various aspects of
ultrasound triggered IGDD. Ultrasound triggered IGDD has
been shown to be feasible (1,2), and initial clinical
applications have started. (Real-time) molecular imaging
methods based on MRI, optical and ultrasound, are used
for guidance of actions to release or activate drugs
and/or permeabilize membranes, and for evaluation of
biodistribution, PK/PD. MRI offers many advantages in
this field such as: excellent target definition,
temperature monitoring, nanoparticle monitoring,
biomarkers for drug release, and biomarkers for BBB
opening.
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14:30
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0448.
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Assessment of atherosclerotic burden using a novel
tropoelastin-specific MR contrast agent
Alkystis Phinikaridou1, Sara Lacerda1,
Begoña L Plaza1, Marcelo Andia2,
and René M Botnar1
1Biomedical Engineering, King's College
London, London, United Kingdom, 2Radiology,
Pontificia Universidad Católica de Chile, Santiago,
Chile
The extracellular matrix protein (ECM) elastin
contributes to 30% of the dry weight of the vascular
wall. Vascular injury leads to de novo synthesis of
tropoelastin molecules, the precursor of cross-linked
mature elastin. Cross-linking has been shown to be
inhibited in the presence of inflammation and
low-density lipoproteins (LDL), both hallmarks of
atherosclerosis and plaque instability. The accumulation
of tropoelastin molecules in the pathologically altered
vessel wall thus, may serve as a new imaging biomarker
to detect atherosclerosis, and potentially plaque
instability [1-4]. In this study, we developed a novel
tropoelastin-specific MR contrast agent and investigated
its merits to quantify disease progression in a murine
model of accelerated of atherosclerosis.
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14:42
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0449.
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Development of nitroxide-based theranostics probes for brain
redox research by MRI
Miho C Emoto1, Shingo Sato2, and
Hirotada G Fujii1
1Sapporo Medical Univeristy, Sapporo, Japan, 2Yamagata
University, Yonezawa, Japan
Theranostics probes, which have both therapeutic and
diagnostic imaging capabilities in one dose, show great
promise for use in MRI examinations. In the present
study, we synthesized nitroxide-based theranostics
probes by connecting anti-inflammatory drugs, ibuprofen
and ketoprofen, to nitroxides that act as T1 contrast
agents in MRI. MRI of mouse heads after injection of
these synthesized probes showed that they worked as T1
contrast agents in mouse brains. Production of nitric
oxide in septic mouse brains was remarkably inhibited by
the addition of these probes, indicating that they
also acted as anti-inflammatory drugs.
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14:54
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0450.
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Initial Experience in a Pilot Study of Blood-Brain Barrier
Opening for Chemo-Drug Delivery to Brain Tumors by MR-Guided
Focused Ultrasound
Yuexi Huang1, Ryan Alkins2, Martin
Chapman3, James Perry4, Arjun
Sahgal5, Maureen Trudeau6, Todd
Mainprize7, and Kullervo Hynynen1,2
1Sunnybrook Research Institute, Toronto, ON,
Canada, 2Department
of Medical Biophysics, University of Toronto, Toronto,
ON, Canada, 3Department
of Anaesthesia, Sunnybrook Health Sciences Centre,
Toronto, ON, Canada, 4Division
of Neurology, Sunnybrook Health Sciences Centre,
Toronto, ON, Canada, 5Department
of Radiation Oncology, Sunnybrook Health Sciences
Centre, Toronto, ON, Canada, 6Division
of Medical Oncology and Hematology, Sunnybrook Health
Sciences Centre, Toronto, ON, Canada, 7Division
of Neurosurgery, Sunnybrook Health Sciences Centre,
Toronto, ON, Canada
In the first case of a pilot clinical study to establish
the feasibility, safety and preliminary efficacy of
focused ultrasound to temporarily open blood brain
barrier (BBB) to deliver chemotherapy to brain tumors,
BBB was successfully opened at two targeted volumes
close to the peripheral margin of the tumor,
approximately 4cm lateral from the midline of the brain.
This may provide a new way to deliver therapeutic agents
into brain for the treatment of tumors and other brain
diseases.
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15:06
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0451.
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Development of Gadoxetate DCE-MRI to Evaluate Liver
Transporter Function: Reproducibility of Established
Technique and Application in OATP KO Rats
Apoorva Mondal1, Xiangjun Meng2,
Richard Kennan3, Jocelyn Yabut4,
Cristian Salinas5, and Catherine D. G. Hines2
1Telecommunications Engineering, University
of Maryland-College Park, College Park, MD, United
States, 2Translational
Imaging Biomarkers, Merck Research Laboratories, West
Point, PA, United States,3Translational
Imaging Biomarkers, Merck Research Laboratories,
Kenilworth, NJ, United States, 4Pharmacokinetics,
Merck Research Laboratories, Rahway, NJ, United States, 5Biogen,
Inc., Cambridge, MA, United States
Recently, Ulloa et al described a compartmental modeling
approach to measure gadoxetate influx and efflux as a
potential biomarker of hepatobiliary transporter
function, as uptake and efflux are mediated by known
transporters. The purpose of this study was to reproduce
the described acquisition and post-processing, and apply
the MRI assay to variations of liver influx transporter
Oatp1a/1b knock-out (KO) rats to potentially
differentiate between degrees of transporter function.
In vivo results demonstrate significant differences in
influx constants between groups of KO rats, and that
this assay may be suitable for investigating
drug-induced liver injury and drug-drug interactions.
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15:18
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0452.
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MRI assessment of Changes in Tumor Oxygenation post
Hypoxia-targeted Therapy
Shubhangi Agarwal1, Troy Kozlowski1,
Rohini Vidya Shankar1, Landon J. Inge2,
and Vikram D. Kodibagkar1
1SBHSE, Arizona State University, Tempe, AZ,
United States, 2St.
Joseph's Hospital and Medical Center, Phoenix, AZ,
United States
Solid tumors have hypoxic foci that be targeted using
hypoxia activated/targeting drugs. Utilizing
quantitative MR oximetry techniques such as the PISTOL
(Proton Imaging of Siloxanes to map Tissue Oxygenation
Levels) technique could allow for patient stratification
for personalized therapy. This study uses the PISTOL
technique to evaluate how the hypoxia activated drug TPZ
(Tirapazamine) depends on and affects the oxygenation
and edema fraction of epidermoid carcinoma (A431) and
non-small cell lung cancer (H1975). Surprisingly, TPZ
was more effective on the H1975 tumors than A431, in
spite of higher pre-treatment pO2 levels, potentially
due to perfusion-related differences in tumor drug
delivery.
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15:30
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Adjournment & Meet the
Teachers |
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