At home monitoring for 177Lu DOTATATE treatment personalization

对于转移性生长抑素受体2（SSTR 2）阳性神经内分泌肿瘤（NET）患者， 使用177 Lu-DOTATATE的靶向治疗大大增加了无进展生存期（PFS），如在 NETTER-1试验。对于用177 Lu处理的中肠NET，第20个月的PFS为65.2%（95%CI，50.0 - 76.8）。 DOTATATE+奥曲肽，而接受60 mg的对照组为10.8%（95% CI，3.5 - 23.0） 奥曲肽长效释放每4周。现在，177 Lu-DOTATATE已获得FDA批准， 成为有症状NET患者和转移性扩散患者的标准治疗。但FDA 包装说明要求患者接受四次7.4 GBq治疗，无论大小，体重，性别或 患者健康状况。传统上，靶向放射性核素疗法是基于对患者的剂量来个性化的。 主要器官处于危险之中。标准化治疗与个性化医疗的理想背道而驰， 对于许多患者来说，这是非最佳治疗剂量。这项提议的科学前提是， 准确评估危及器官的剂量将使治疗个性化并改善结果 超过所建议的护理标准（即，4×7.4 GBq 177 Lu-DOTATATE）方案。 在目标1中，从可穿戴、低成本、多探测器测量个体器官剂量信息的方法 个性化的家庭剂量测定（MDPHD）背心将使用蒙特卡罗模拟工具。在目标2中，a 将制作用于器官特异性剂量估计的原型MDPHD背心。背心将包括6-15个小， 光谱计数检测器，重量在480-750克之间，这取决于 探测器安装在背心上。它将被设计成重量轻，形式拟合，并将有对齐 能够使背心相对于患者的内部环境保持一致的日常穿着/定位的特征 机关每天戴上、对准和收集数据的时间将少于8分钟。背心还将 配备电子设备，可以通过Wi-Fi获取，存储和发送数据到安全的网站真实的 时间数据监控在目标3中，一项小型试点研究，使用 流线型协议（即，一次SPECT/CT结合24小时后的门诊MDPHD背心测量， 治疗和每天在家MDPHD背心测量7-21天）与3个时间点（即，第1、4和7天） 临床SPECT/CT成像（即，许多非美国国家遵循标准方案）。在 本项目结束时，创建和利用MDPHD背心的方法将经过测试和验证， MDPHD背心将准备用于更大的患者队列的评估。

For patients with metastatic, somatostatin-receptor-2 (SSTR2) positive neuroendocrine tumors (NETs), targeted therapy using 177Lu-DOTATATE greatly increases progression-free survival (PFS), as shown in the NETTER-1 trial. PFS at month 20 was 65.2% (95% CI, 50.0 - 76.8) for midgut NETs treated with 177Lu- DOTATATE plus octreotide compared to 10.8% (95% CI, 3.5 - 23.0) in a control group receiving 60 mg octreotide long-acting release every 4 weeks. Now that 177Lu-DOTATATE has FDA approval it will likely become the standard of care for symptomatic NET patients and those with metastatic spread. However, FDA package instructions call for patients to receive four 7.4 GBq treatments, regardless of size, weight, gender or patient health status. Traditionally, targeted radionuclide therapies are personalized based upon dose to the main organs at risk. Standardized therapy is counter to the ideals of personalized medicine and will lead to non-optimum therapeutic dosing for many patients. The scientific premise of this proposal is that practical tools to accurately assess dose to organs at risk will enable treatment personalization and improve outcomes beyond the proposed standard of care (i.e., 4×7.4 GBq 177Lu-DOTATATE) protocol. In Aim 1 methods to measure individual organ dose information from a wearable, low cost, multi-detector personalized home dosimetry (MDPHD) vest will be developed using Monte Carlo simulation tools. In Aim 2, a prototype MDPHD vest for organ specific dose estimation will be fabricated. The vest will consist of 6-15 small, spectrographic counting detectors and weigh between 480-750 grams depending upon the number of detectors incorporated into the vest. It will be designed to be light weight, form fitting and will have alignment features to enable consistent day to day wearing/positioning of the vest with respect to the patient's internal organs. Time to put on, align and collect data will be less than 8 minutes each day. The vest will further be equipped with electronics that can acquire, store and send the data via Wi-Fi to a secure web-site for near real time data monitoring. In Aim 3, a small pilot study to compare individual organ dosimetry estimates using a streamlined protocol (i.e., one SPECT/CT combined with an in-clinic MDPHD vest measurement at 24-hr post- therapy and daily at-home MDPHD vest measurements for 7-21 days) versus 3-time point (i.e., 1, 4 and 7 day) in-clinic SPECT/CT imaging (i.e., standard protocol followed in many non-US countries) will be conducted. At the end of this project, methods to create and utilize a MDPHD vest will have been tested and validated and the MDPHD vests will be ready for evaluation on a larger patient cohort.