MRI of Iron-labeled Microsphere Biodistribution for Radioembolization Dosimetry

描述（由申请人提供）：对于不可切除的肝细胞癌（HCC）和肝脏转移患者，钇-90 （90Y）放射栓塞是一种强有力的新治疗选择。放射栓塞包括导管定向输注90Y微球，为肝脏肿瘤提供内部辐射剂量。无法非侵入性地表征这些球体的异质生物分布使得患者特异性剂量优化变得困难。剂量选择不当可降低治疗效果或导致健康肝组织的意外破坏。本提案的目的是开发一种新的磁共振成像（MRI）技术，以无创量化90Y微球的生物分布，以优化患者特异性剂量。超顺磁性氧化铁（SPIO）标记允许在导管定向递送微胶囊和栓塞颗粒期间进行体内MRI可视化。R2*测量可用于SPIO颗粒浓度的非侵入性定量。我们建议用SPIO标记90Y微球，以便在体内定量微球的生物分布。我们需要优化spio标记的微球组成，开发自由呼吸的高分辨率方法来精确测量体内R2*，并最终验证这些方法可以准确定量90Y微球的生物分布。我们提出的项目将在幻影和动物模型研究中解决以下具体目标：具体目标1：表征90Y微球SPIO含量与相关R2*弛豫特性之间的关系，并优化内容，使R2*的变化与球体浓度成正比。具体目标2：开发一种高分辨率的自由呼吸采集策略（“自旋回波的梯度回波采样”PROPELLER方法），以提高体内肝内R2*测量的准确性。具体目的3：验证spio标记微球可以精确量化宏观肝内生物分布，以测量肿瘤与正常（T/N）分布比。特异性目标4：验证spio标记微球允许准确的体内定量肿瘤内生物分布，以描述靶向肿瘤内的空间依赖性剂量变化。

DESCRIPTION (provided by applicant): 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.