Abstract: Five Eleven Pharma is developing a novel radiotracer, [68Ga]P15-041, to facilitate Positron Emission Tomography (PET) detection of bone cancer. Our Phase 0/I feasibility and dosimetry clinical trial in metastatic prostate cancer patients (IND 129870) was well received by the FDA who provided guidance on an expanded effort at this early phase to determine near optimum dose regimen and imaging parameters. 511P has funded this clinical study through its own resources. Using this company funded trial data, this Phase I SBIR application will specifically support the imaging/analytical data assessment required to answer the FDA?s question, to allow the company to move into Phase II/III clinical trials next year. This project supports an innovative new bone imaging agent, [68Ga]P15-041, that utilizes a well known ligand, (HBED) in conjunction with the leading bone targeting agent (bisphosphonate), to specifically target cancerous bone lesions. This novel radiotracer should allow for the broader adoption of highly targeted, low-radiation, short lived 68Ga imaging agents for bone cancer. The early detection of cancer and metastatic disease is paramount to improving cancer outcomes, and 68Ga imaging agents, such as [68Ga]P15-041 have a number of clear advantages, such as short half-life, decay by positron emission and generator-based radionuclide production, that will support a broader adoption and use of these PET enhancing radiotracers. To support the FDA?s request, Aim 1 will determine the optimal radiopharmaceutical dose and scan time to preserve diagnostic accuracy while minimizing patient exposure. We will sub-sample the list mode PET data from our metastatic prostate cancer study to simulate injected dose, scan time after injection, and scan duration. We will use data acquired from patients following a 370 MBq (10 mCi) dose using a list-mode acquisition on a Philips Ingenuity PET/CT scanner, and then sub-sample the data to emulate lower dose injections using published bootstrapping methods to create 20 replicates for each dose we wish to evaluate; we plan to generate replicates corresponding to 74, 185, and 259 MBq (2, 5, and 7 mCi), in addition to the data set at 370 MBq (10 mCi) injection. We will use Time of Flight (TOF) reconstruction methods, as this leads to improved detectability and more accurate recovery of lesion uptake, with lower variability. We expect to determine the dependence of lesion VOI bias and precision to decreasing injected dose which will allow us to determine the optimized injected dose, scan time and scan duration that optimizes diagnostic acccuracy (lesion detection) while minimizing patient radiation exposure. In Aim 2, we will evaluate all Phase 0/I clinical data, including drug pharmacokinetics, safety, radiation dosimetry and other pertinent information, to create a report of clinical findings in preparation for meeting with the FDA to plan additional studies. Successful completion of these aims will provide a clear path forward for future studies needed to obtain NDA approval. Page 1 of 1