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

开发可穿戴技术，实现 177Lu DOTATATE 神经内分泌肿瘤治疗的个性化

• 批准号: 10010282
• 负责人: Larry Pierce
• 金额: $ 26.29万
• 依托单位: PRECISION SENSING, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10010282
• 关键词: Age; Asia; Attenuated; Australia; Clinic; Clinic Visits; Control Groups; Country; Data; Development; Devices; Diagnosis; Dose; Electronics; Electrons; Europe; Evaluation; FOLH1 gene; Gender; Goals; Half-Life; Health Status; Home environment; Hour; Image; Incidence; Individual; Infusion procedures; Instruction; Isotopes; Kidney; Kinetics; Lead; Letters; Liver; Location; Measurement; Measures; Methodology; Methods; Midgut; Monitor; Monte Carlo Method; Neuroendocrine Tumors; Octreotide; Organ; PET/CT scan; Patients; Pharmaceutical Preparations; Photons; Physicians; Pilot Projects; Positioning Attribute; Progression-Free Survivals; Protocols documentation; Publishing; Radiation therapy; Radionuclide therapy; Resources; Risk; Secure; Spleen; Standardization; Structure; Techniques; Technology; Testing; Therapeutic; Time; Toxic effect; Treatment Protocols; United States; Visit; Weight; Work; X-Ray Computed Tomography; base; cost; design; detector; dose information; dosimetry; early phase clinical trial; imaging study; improved; improved outcome; individualized medicine; interest; internal radiation; light weight; personalized medicine; precision medicine; prototype; response; serial imaging; sex; side effect; single photon emission computed tomography; somatostatin receptor 2; standard of care; targeted treatment; theranostics; therapeutic effectiveness; tool; treatment optimization; tumor; wearable device; web site; wireless fidelity

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.

对于转移性，生长抑素受体-2（SSTR2）阳性神经内分泌肿瘤（NETS）的患者， 使用177LU-葡萄糖的靶向治疗大大增加了无进展的生存（PFS），如图所示 Netter-1试验。第20个月的PFS为65.2％（95％CI，50.0-76.8），用于177lu- 单独使用dotatate，而接受60 mg Octreotide长的对照组中为10.8％（95％CI，3.5-23.0） 每4周释放一次表演。现在，177lu-dotatate已获得FDA批准，它可能会成为标准 有症状的净患者和转移性扩散患者的护理。但是，FDA包说明 呼吁患者接受四种7.4 GBQ治疗，无论大小，体重，性别或患者健康状况如何。 传统上，有针对性的放射线疗法是根据对有风险的主要器官的剂量进行个性化的。 标准化疗法与个性化医学的思想相反，将导致非优势 许多患者的治疗剂量。 177LU的器官剂量测定方法的传统方法（即6.65 白天的半衰期）需要3-4个纵向成像会话，以超过7天的时间。这很昂贵，利用了 大量的诊所资源，对患者来说是朴素的。该项目的目的是确切 个性化的177lu-介酸器官剂量测定法而无需串行成像会话（注意：主要 约98％接受177lu-磷酸治疗的患者的OAR是肾脏）。我们将通过 开发廉价，可穿戴的监控技术，以允许定量测量 病人在家。这将支持对处于危险（OAR）的单个器官（OAR）的清洗的准确估计， 为每个治疗课程启用准确的器官剂量法，从而使医生可以单独量身定制 基于个性化器官剂量法信息的治疗数量。在AIM 1方法中 来自可穿戴，低成本的个性化家用剂量法（PHD）皮带的单个器官剂量信息将是 使用蒙特卡洛模拟工具开发。在AIM 2中，特定器官剂量的原型博士带 估计将被制造。皮带将由6-15个小光谱学计数和重量组成 <750克，具体取决于掺入皮带的检测器数量。它将设计为轻巧 重量，形式配件，并具有对齐功能，以使日常持续佩戴/定位 皮带相对于患者的内脏器官。皮带将进一步配备可以 通过Wi-Fi获取，存储并将数据发送到安全的Web站点，以进行近实时数据监视。在AIM 3中 小型试点研究，以使用简化的方案比较单个器官剂量测定法（即 输注后24小时加上SPECT/CT和PHD皮带测量，以及家庭测量时的7-21 phD带） 与3个时间点（即1、4和7天）在临界SPECT/CT成像（即，在许多人中进行标准方案 非美国国家）将进行。在该项目的结尾，创建和使用博士带的方法将 已经经过测试和验证，博士带准备在早期临床试验中进行评估。