MRI of Iron-labeled Microsphere Biodistribution for Radioembolization Dosimetry

描述（由申请方提供）：钇-90（90 Y）放射栓塞是不可切除肝细胞癌（HCC）和肝转移患者的一种强大的新治疗选择。放射性栓塞涉及导管引导的90 Y微球输注，其向肝肿瘤提供内部放射剂量。无法无创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。剂量选择不当会降低治疗效果或导致健康肝组织的意外破坏。该提案的目的是开发一种新的磁共振成像（MRI）技术，以非侵入性地量化90 Y微球的生物分布，用于患者特定的剂量优化。 超顺磁性氧化铁（SPIO）标记允许在微胶囊和栓塞颗粒的导管定向递送期间进行体内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90 Y微球，以允许在体内定量微球的生物分布。我们需要优化SPIO标记的微球组成，开发自由呼吸的高分辨率方法，用于精确的体内R2* 测量，并最终验证这些方法允许准确定量90 Y微球生物分布。我们提出的项目将在体模和动物模型研究中解决以下具体目标：具体目标1：表征90 Y微球SPIO含量与相关R2* 弛豫率特性之间的关系，并优化含量，使R2* 变化与球体浓度成比例。具体目标二：开发一种高分辨率自由呼吸采集策略（“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。具体目标3：验证SPIO标记微球允许准确定量肉眼可见的肝内生物分布，以测量肿瘤与正常（T/N）分布比。具体目标4：验证SPIO标记的微球允许准确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。 公共卫生相关性：放射性栓塞是一种肝癌治疗方法，涉及靶向注射小放射性玻璃珠来治疗肿瘤。然而，空间分布变化可能使个体化、患者特异性剂量选择变得相当困难。跟踪微珠分布的新成像方法应允许剂量优化以改善临床结局。

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.