At home monitoring for 177Lu DOTATATE treatment personalization

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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.