DESCRIPTION (provided by applicant): Positron Emission Tomography (PET) is a unique imaging technique among the many diagnostic protocols available to clinicians. Unlike techniques such as X-ray, SPECT, CT, ultrasound, MRI, or mammography that provide imaging of solid anatomical features, PET provides a solitary focus on the metabolic profile of the tissue being imaged. In spite of the unique information provided by PET imaging in the diagnosis, staging and disease monitoring of cancer, more widespread use of this technology is hampered by the dearth of approved imaging agents. Currently, only a single agent, 18F fluorodeoxyglucose (18F-FDG), is widely used for PET imaging studies. However, positron-emitting isotopes of copper, such as 62Cu or 64Cu, are promising radioisotopes for PET imaging and offer a number of advantages, including simple coordination chemistry with numerous ligands to allow use in a variety of clinical applications. Among these specialized radiopharmaceutical compounds is hypoxia-specific agent 64Cu-ATSM, which has demonstrated clear advantages over other hypoxia-specific imaging agents. Unfortunately, the current method of synthesizing this compound is not feasible for multi-site clinical use, results in considerable operator radiation dose, and gives an undesirable ethanol-based injection solution. Based on the experience of Proportional Technologies, Inc. (PTI) in the manufacture of lyophilized kits for synthesis of Cu radiopharmaceuticals, we propose that this technology be extended to the development an H2ATSM kit compatible for use with 64Cu. This will be accomplished through expansion and adaption of PTI's currently developed method of manufacturing H2ATSM kits for use with 62Cu to overcome the technical challenges presented by the longer-lived 64Cu isotope. The primary foci of the project will be increasing the concentration of available ligand to accommodate greater levels of radioactivity while preserving a reasonable injection volume and maintaining ligand solubility. The availability of 64Cu-ATSM in a manner appropriate for multi-site clinic use would supplement the use of 18F- FDG for imaging tumors and expand the battery of PET imaging agents available to the clinician. The development of a robust, widely-available PET imaging agent for tumor hypoxia is especially important since hypoxic tumors are generally resistant to traditional treatment methods and are often associated with poor prognosis. Identifying this trait as early as possible through the use of 64Cu-ATSM would assist patients and physicians in diagnosing and managing disease. PUBLIC HEALTH RELEVANCE: This project involves developing an improved means of manufacturing the radioactive pharmaceutical compound (radiopharmaceutical) 64Cu-ATSM. This radiopharmaceutical is used when conducting Positron Emission Tomography (PET) imaging scans to identify tumor hypoxia and allow physicians to more effectively manage a patient's treatment options.