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 这个第一阶段的研究项目将开发一种生长抑素受体靶向的62铜放射性药物 用于正电子发射断层扫描（PET）神经内分泌肿瘤的临床成像。短- 活性62 Cu放射性标记可随时重复用于按需放射性药物标记 通过Proportional公司开发的紧凑型模块化62 Zn/62 Cu放射性核素发生器系统 技术公司生长抑素受体被发现在大多数神经内分泌系统中高度表达， 肿瘤，并且是PET检测这些恶性肿瘤的成熟分子靶点， 68 Ga标记的受体靶向肽家族，已在国外广泛临床使用， 美国.该项目将开发神经内分泌肿瘤PET成像的替代方法， 使用62 Cu-DOTA-TATE作为放射性药物，其可以容易地用于评估 肿瘤负荷，同时仍然允许立即独立的18F-FDG PET评估肿瘤 侵略性，从而更充分地表征个人的疾病状态。62 Cu-DOTA-TATE还将 由于相对较低的患者辐射，对儿科神经内分泌肿瘤成像具有吸引力 当用这种短寿命的核素成像时暴露。我们的商业化方法将是寻求 FDA批准我们的62 Cu发生器和配套无菌套件的组合， 要求技术专家在即将进行62 Cu-DOTA-TATE放射性药物配制之前 注射对于这个第一阶段项目，我们的具体目标是：（1）生产和验证冻干试剂盒 用于62 Cu-DOTA-TATE的按需临床现场配混的制剂;和（2）评价62 Cu-DOTA-TATE的临床应用。 DOTA-TATE在人体内的分布、药代动力学和剂量测定。此外，可行性 全身62 Cu-DOTA-TATE肿瘤成像将通过直接比较62 Cu-DOTA-TATE和62 Cu-DOTA-TATE来记录。 使用111 In-OctreoScan SPECT或68 Ga-DOTA-NOC获得的同期临床检查结果 彼前这些第1阶段实验预期将证明62 Cu-DOTA-TATE可以可靠地且 以高放射化学纯度稳健地复合，且全身62 Cu-DOTA-TATE PET 似乎适合临床神经内分泌肿瘤成像，从而为 II期研究，旨在评估62 Cu-DOTA-TATE PET/CT在患者管理中的有效性。