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

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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.