MRI of Iron-labeled Microsphere Biodistribution for Radioembolization Dosimetry

说明(申请人提供)：~(90)Y放射栓塞术是治疗不能切除的肝细胞癌和肝转移患者的一种强有力的新治疗选择。放射栓塞术包括在导管引导下注入90Y微球，这些微球为肝脏肿瘤提供内部辐射剂量。由于无法非侵入性地表征这些球体的异质生物分布，使得患者特定剂量的优化变得困难。剂量选择不当可能会降低治疗效果或导致对健康肝组织的意外破坏。这项建议的目的是开发一种新的磁共振成像(MRI)技术，以非侵入性量化90Y微球的生物分布，以实现患者特定剂量的优化。超顺磁性氧化铁(SPIO)标记可以在导管引导的微囊和栓塞剂颗粒输送过程中实现体内MRI可视化。R2*测量可用于SPIO颗粒浓度的非侵入性量化。我们建议用SPIO标记90Y微球，以允许在体内定量微球的生物分布。我们需要优化SPIO标记的微球成分，开发自由呼吸的高分辨率方法来精确地在体内测量R2*，并最终验证这些方法可以准确量化90Y微球的生物分布。我们建议的项目将在模体和动物模型研究中解决以下特定目标：特定目标1：表征90Y微球SPIO含量与相关R2*弛豫性能之间的关系，并优化含量，使R2*变化与球体浓度成正比。具体目标2：开发一种高分辨率自由呼吸采集策略(自旋-回声螺旋桨方法的梯度回波采样)，以提高活体肝内R2*测量的准确性。具体目标3：验证SPIO标记的微球可以准确定量宏观的肝内生物分布，以测量肿瘤与正常(T/N)的分布比率。具体目标4：验证SPIO标记的微球可以在体内准确定量肿瘤内的生物分布，以描述目标肿瘤内空间相关的剂量变化。 与公共卫生相关：放射栓塞术是一种肝癌治疗方法，包括靶向注射小放射性玻璃微珠来治疗肿瘤。然而，空间分布的差异可能会使个性化的、针对患者的剂量选择变得非常困难。追踪珠子分布的新成像方法应该允许优化剂量以改善临床结果。

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.