Development of wearable technology to enable therapy personalization of 177Lu DOTATATE for neuroendocrine tumors

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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 alone 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 likely will 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. Traditional methods for organ dosimetry estimation for 177Lu (i.e., 6.65 day half-life) require 3-4 longitudinal imaging sessions spread out over ~7 days. This is expensive, utilizes a lot of clinic resources and is burdensome to the patient. The goal of this project is to enable precise individualized 177Lu-DOTATATE organ dosimetry without requiring serial imaging sessions (note: the main OAR for ~98% of patients receiving 177Lu-DOTATATE therapy is the kidneys). We will accomplish this by developing inexpensive, wearable monitoring technology to allow quantitative measurements to be made by the patient at home. This will support accurate estimation of the washout from individual organs at risk (OAR), enabling accurate organ dosimetry for each treatment session thereby allowing physicians to individually tailor the number of treatments based upon personalized organ dosimetry information. In Aim 1 methods to measure individual organ dose information from a wearable, low cost, personalized home dosimetry (PHD) belt will be developed using Monte Carlo simulation tools. In Aim 2, a prototype PHD belt for organ specific dose estimation will be fabricated. The belt will consist of 6-15 small, spectrographic counting detectors and weigh <750 grams depending upon the number of detectors incorporated into the belt. 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 belt with respect to the patient’s internal organs. The belt 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 and PHD belt measurement at 24 hr post infusion plus 7-21 PHD belt at home measurements) 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 PHD belt will have been tested and validated and the PHD belt will be ready for evaluation in an early phase clinical trial.