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.
Statement of Relevance This project will advance public health by development of an imaging technology that improves detection of neuroendocrine tumors, as well as physician's ability to plan appropriate treatment of patients with neuroendocrine cancer. The proposed tumor-targeted copper-62 radiopharmaceutical can be commercially distributed to any clinical PET imaging facility in the United States, relying on a longer-lived zinc-62/copper-62 parent/daughter radionuclide generator system already developed by Proportional Technologies, Inc., thereby providing universal patient access to receptor-based PET neuroendocrine tumor imaging.
