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

项目摘要 这一阶段的研究项目将开发一种以生长抑素受体为靶点的62Cu-放射性药物 用于临床神经内分泌肿瘤的正电子发射断层扫描(PET)成像。简而言之- Live62Cu放射性标记可随时重复用于按需放射性药物标记 通过按比例开发的紧凑型模块化62Zn/62Cu放射性核素发生器系统 技术公司发现大多数神经内分泌都高度表达生长抑素受体 肿瘤，是PET检测这些恶性肿瘤的一个公认的分子靶点。 已在国外广泛应用的68Ga标记受体靶向多肽家族 美国。该项目将开发一种替代神经内分泌肿瘤的PET成像方法， 用~(62)Cu-DOTA-Tate作为一种易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肿瘤评估 攻击性，因此更充分地表征了个人的疾病状态。62Cu-DOTA-Tate也将 由于相对较低的患者辐射，在儿科神经内分泌肿瘤成像方面具有吸引力 使用如此短命的核素进行成像时的暴露。我们的商业化方法将是寻求 FDA批准了我们的62Cu发生器和配套的无菌试剂盒的组合，该试剂盒允许- 紧随其后的62Cu-DOTA-Tate放射性药物的需求技术人员合成 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 按需临床现场配制62CuDOTA-Tate的配方；和(2)评价62CuDOTA-Tate DOTA-Tate在人体内的分布、药代动力学和剂量学。此外，还探讨了 62Cu-DOTA-Tate全身肿瘤成像将通过与62Cu-DOTA-Tate的直接比较来记录 111In-OctreoScan SPECT或68Ga-DOTA-NOC同期临床检查结果 宠物。这些第一阶段的实验有望证明62Cu-DOTA-Tate可以可靠地和 在高放化纯度下强健合成，全身62Cu-DOTA-Tate PET 似乎适合于临床神经内分泌肿瘤的成像，从而为 第二阶段的研究是评估62Cu-DOTA-Tate PET/CT在患者管理中的效果。

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.