Receptor-Targeted Neuroendocrine Tumor Imaging with Generator-Produced Cu-62

使用发生器产生的 Cu-62 进行受体靶向神经内分泌肿瘤成像

• 批准号: 9200463
• 负责人: JEFFREY L LACY
• 金额: $ 21.86万
• 依托单位: PROPORTIONAL TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9200463
• 关键词: Aggressive behavior; Biodistribution; Cancer Patient; Chemistry; Child; Clinical; Clinical assessments; Companions; Copper; Data; Daughter; Detection; Development; Diagnosis; Diagnostic Procedure; Disease; Drug Kinetics; Evaluation; FDA approved; Family; Formulation; Foundations; Half-Life; Hospitals; Hour; Human; Image; Imaging technology; In 111 Pentetreotide; Individual; Injection of therapeutic agent; Label; Lesion; Life; Location; Malignant Neoplasms; Manufacturer Name; Measures; Medical; Molecular Target; Nature; Neoplasms; Neuroblastoma; Neuroendocrine Tumors; Neurosecretory Systems; Orphan Drugs; Parents; Patient Care; Patients; Pediatrics; Peptides; Pharmaceutical Preparations; Phase; Physicians; Positron-Emission Tomography; Property; Public Health; Radiation; Radiolabeled; Radiometry; Radionuclide Generators; Radiopharmaceuticals; Recruitment Activity; Research; Research Project Grants; Role; Schedule; Site; Somatostatin Receptor; Sterility; System; Technology; Therapeutic; Tracer; Tumor Burden; United States; X-Ray Computed Tomography; Zinc; base; cancer imaging; clinical research site; commercialization; diagnostic accuracy; dosimetry; improved; manufacturing facility; medulloblastoma; patient population; pediatric patients; phase 1 study; phase 2 study; radiochemical; radiotracer; receptor; research clinical testing; research study; single photon emission computed tomography; standard of care; tumor; uptake

Project Summary This Phase 1 research project will develop a somatostatin-receptor-targeted 62Cu- radiopharmaceutical for clinical imaging of neuroendocrine tumors with positron emission tomography (PET). The short- lived 62Cu radiolabel is readily and repeatedly available for on- demand radiopharmaceutical labeling via a compact modular 62Zn/ 62Cu radionuclide generator system developed by Proportional Technologies, Inc. Somatostatin receptors are found to be highly expressed by most neuroendocrine tumors, and are a well-established molecular target for PET detection of these malignancies with a family of 68Ga-labeled receptor-targeted peptides that have come into widespread clinical use outside the USA. This project will develop an alternative approach to PET imaging of neuroendocrine tumors, employing 62Cu-DOTA-TATE as a radiopharmaceutical that can readily be employed for assessment of tumor burden, while still allowing immediate independent 18F-FDG PET assessment of tumor aggressiveness, thus more fully characterizing the individual's disease state. 62Cu-DOTA-TATE will also be attractive for neuroendocrine tumor imaging in pediatrics, due to relatively low patient radiation exposure when imaging with such a short-lived nuclide. Our commercialization approach will be to seek FDA approval for the combination of our 62Cu-generator, and a companion sterile kit that allows on- demand technologist compounding of the 62Cu-DOTA-TATE radiopharmaceutical immediately prior to injection. For this Phase 1 project our Specific Aims are: (1) to produce and validate a lyophilized kit formulation for on-demand, clinical-site compounding of 62Cu-DOTA-TATE; and (2) to evaluate 62Cu- DOTA-TATE distribution, pharmacokinetics and dosimetry in humans. Additionally, the feasibility of whole-body 62Cu-DOTA-TATE tumor imaging will be documented by direct comparison of 62Cu- findings to contemporaneous clinical exams obtained with 111In-OctreoScan SPECT or 68Ga-DOTA-NOC PET. These Phase 1 experiments are expected to demonstrate that 62Cu-DOTA-TATE can be reliably and robustly compounded at high radiochemical purity, and that whole-body 62Cu- DOTA-TATE PET appears suitable for clinical neuroendocrine tumor imaging, thereby establishing the foundation for Phase 2 studies to assess the efficacy of 62Cu-DOTA-TATE PET/CT in patient management.

项目摘要 该阶段1研究项目将开发一个靶向生长抑制剂的62cu- radiopharmaceutical 用于神经内分泌肿瘤的临床成像，具有正电子发射断层扫描（PET）。短 - 居住的62cu radiolabel很容易且重复用于射线类药物标签 通过紧凑的模块化62zn/ 62cu放射性核素发生器系统由比例开发 Technologies，Inc。大多数神经内分泌的生长抑素受体高度表达 肿瘤，是一个公认的分子靶标，用于宠物检测这些恶性肿瘤 由68GA标记的受体定价肽的家族，在外面广泛临床使用 美国。该项目将开发一种替代方法来进行神经内分泌肿瘤的宠物成像， 采用62cu-dota-tate作为可容易用于评估的放射性药物 肿瘤负担，同时仍允许立即独立的18F-FDG PET评估肿瘤 侵略性，因此更充分地表征了个人疾病状态。 62cu-dota-tate也将 由于患者辐射相对较低，对儿科中神经内分泌肿瘤成像具有吸引力 用如此短的核素成像成像时暴露。我们的商业化方法是寻找 FDA批准了我们的62CU发电机的组合和一个伴随的无菌套件 要求技术专家在62cu-dota-tate放射性药物的复合之前立即进行 注射。对于此阶段1项目，我们的具体目的是：（1）生产和验证冻干套件 按需的配方，临床部位复合62cu-dota-tate； （2）评估62cu- 人类中的DOTA-TATE分布，药代动力学和剂量法。另外，可行性 全身62cu-dota-tate肿瘤成像将通过62cu-的直接比较记录 通过111in-Octreoscan SPECT或68GA-DOTA-NOC获得的同期临床检查的结果 宠物。这些阶段1实验有望证明62cu-dota-tate可以可靠，并且 在高放射化学纯度上加重了加剧，全身62cu- dota-tate PET 似乎适用于临床神经内分泌肿瘤成像，从而为 第2阶段的研究评估62CU-DOTA-TATE PET/CT在患者管理中的功效。