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.
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.
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