Yttrium-90 (90Y) radioembolization is a powerful new treatment option for patients with unresectable hepatocellular carcinoma (HCC) and metastases to the liver. Radioembolization involves catheter-directed infusion of 90Y microspheres that provide an internal radiation dose to liver tumors. The inability to non- invasively characterize the heterogeneous biodistribution of these spheres has made patient-specific dose optimization difficult. Poor dose selection can reduce therapeutic efficacy or lead to the unintended destruction of healthy liver tissues. The objective of this proposal is to develop a new magnetic resonance imaging (MRI) technique to non-invasively quantify 90Y microsphere biodistribution for patient-specific dose optimization. Super paramagnetic iron-oxide (SPIO) labeling has permitted in vivo MRI visualization during catheter- directed delivery of microcapsules and embolic particles. R2* measurements can be used for non-invasive quantification of SPIO particle concentrations. We propose labeling 90Y microspheres with SPIO to permit in vivo quantification of microsphere biodistribution. We need to optimize SPIO-labeled microsphere composition, develop free-breathing high-resolution methods for precise in vivo R2* measurements, and ultimately validate that these methods permit accurate quantification of 90Y microsphere biodistribution. Our proposed project will address the following Specific Aims in phantom and animal model studies:
Specific Aim 1 : To characterize the relationship between 90Y microsphere SPIO content and associated R2* relaxivity properties and optimize content such that R2* changes are proportional to sphere concentration.
Specific Aim 2 : To develop a high-resolution free-breathing acquisition strategy ('gradient-echo sampling of the spin-echo'PROPELLER approach) that improves the accuracy of in vivo intra-hepatic R2* measurements.
Specific Aim 3 : To validate that SPIO-labeled microspheres permit accurate quantification of macroscopic intra-hepatic biodistribution for the measurement of tumor-to-normal (T/N) distribution ratios.
Specific Aim 4 : To validate that SPIO-labeled microspheres permit accurate in vivo quantification of intra- tumoral biodistribution for the depiction of spatially dependent dose variations within the targeted tumor.

Public Health Relevance

Radioembolization is a liver cancer therapy involving the targeted injection of small radioactive glass beads to treat the tumor. However, spatial distribution variations can make individualized, patient-specific dose selection quite difficult. New imaging methods to track bead distributions should permit dose optimization to improve clinical outcomes.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Zhang, Huiming
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Northwestern University at Chicago
Schools of Medicine
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