Wearable technology to enable personalization of Lu177-DOTATATE therapy for neuroendocrine tumor patients

Objectives: For patients with metastatic, somatostatin-receptor-2 positive neuroendocrine tumors (NETs), targeted therapy using ¹⁷⁷Lu-DOTATATE greatly increases progression-free survival. Now that ¹⁷⁷Lu-DOTATATE has received FDA approval it likely will become the standard of care for symptomatic NET patients and those with metastatic spread in the United States. However, FDA package instructions call for patients to receive a standardized protocol of four 7.4 GBq treatments, regardless of size or weight. Traditionally, targeted radionuclide therapies are personalized based upon dose to the main organs at risk (OAR, e.g., kidneys, liver, spleen). Standardized therapy is counter to the ideals of personalized medicine and will lead to non-optimum therapeutic dosing for many patients. Traditional imaging-based methods for organ dosimetry estimation for ¹⁷⁷Lu require 3-4 longitudinal imaging sessions spread over 7 days. This is expensive, utilizes a lot of clinic resources and is burdensome to the patient.

Objectives: The goal of this project is to enable precise individualized organ dosimetry without requiring serial imaging sessions. We will accomplish this by developing patient friendly, wearable monitoring technology to allow quantitative measurements to be made by the patient at home. Specifically, we propose a multi-detector personalized home dosimetry (MD PHD) vest that will allow patients to track organ specific radiotracer washout without requiring serial return visits to an imaging clinic. The protocol will still require one SPECT/CT taken 24 hours after administration of ¹⁷⁷Lu-DOTATATE. This will be followed by at home MD PHD vest measurements taken daily for 7 to 21 days. The SPECT/CT measurement provides a quantitative measure of ¹⁷⁷Lu-DOTATATE uptake. The vest measurements provide accurate estimation of the washout from OAR. With this information, physicians can tailor the number of treatments based upon personalized organ dosimetry information.

Methods: The MD PHD vest will utilize a sparse set (e.g., 15) of small detectors (e.g., 1.2 cm³) optimally placed within a personalized vest to collect data from OAR over many days. A CT image will be used to register the vest with a patient’s internal organs. Monte Carlo simulations will be used to determine the sensitivity matrix between a 2D array of detectors surrounding the patient and the patient’s OAR. Optimization methods will be used to select the positioning of detectors around the patient. The patient will wear the vest for 2 minutes once a day for 7-21 days. The basic methodology was tested using Monte Carlo simulation. The testing phantom consisted of a 27cm diameter by 70cm long right circular cylinder. Anthropomorphic objects representing the liver, spleen, right and left kidneys and two tumors (i.e., 2.5 cm and 1.5 cm diameter) were placed in the phantom. The ratios of the activity concentration for liver, spleen, right and left kidneys, and the 2.5 cm and 1.5 cm tumors to background were 2, 10, 10, 8, 48, 60, respectively. The washout rate for liver, spleen, right kidney, left kidney, 2.5 cm tumor, 1.5 cm tumor and background were 74, 66, 40, 46, 92, 96 and 95 hrs, respectively. Tests were run for vests with 15 sensors. Simulated acquisition times were 2 minutes. Activity in each object of interest was decayed appropriately. Poisson resampling was used for accurate noise modeling. Decay rates were estimated using 7 and 21 daily vest measurements.

Results: The root mean square error (RMSE) of the estimated washout rate for each of the OAR and tumors using the optimized 15 sensor vests are provided in Table 1. Using all 21 measurements the RMSE was less than 3.3% for all objects. Using only 7 measurements, the organ estimates were still less than 4% but RMSE increased for the tumors.

Conclusions: Initial simulation studies indicate that a very sparse MD PHD vest can be used to monitor washout from OAR and tumors to enable individualized dosimetry for patients undergoing Lu-177 DOTATATE therapy.

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