Clinical Evaluation of a Novel Prostate Cancer PET Diagnostic

DESCRIPTION provided by applicant Prostate cancer PCa is the most commonly diagnosed cancer and second leading cause of cancer death in American men The utility of the widely accepted diagnostic test for PCa the PSA test has come under severe scrutiny as only of men with PCa have levels that fall within the current PSA reference range Elevated PSA levels are not correlated well with the stage of PCa and a significant number of men are exposed to unnecessary surgery and radiation therapy with concomitant risks and detrimental side effects Molecular imaging of PCa is an increasingly important component for diagnosis staging and treatment of the disease However the FDA has approved only one diagnostic agent for PCa since ProstaScintandquot a mouse monoclonal antibody While the marker that ProstaScintandquot recognizes prostate specific membrane antigen PSMA is ideal as a biomarker ProstaScintandquot binds an intracellular epitope rendering it unable to detect living PCa cells As a result diagnostic accuracy of less than has led to poor adoption of this imaging test by oncologists PSMA a transmembrane protein has been described as an ideal biomarker for PCa diagnosis and targeted therapy as it is expressed mainly in PCa with a prevalence of andgt has high expression levels at all stages of the disease and is upregulated in androgen insensitive and metastatic disease is accessible on the cell surface and not shed into the circulation and is internalized after ligand binding To address the unmet need for accurate and quantitative imaging of PCa we will advance our novel proprietary low molecular weight PSMA inhibitor that selectively delivers an imaging radionuclide to PCa cells This small molecule inhibitor CTT binds PSMA irreversibly at an IC of less than nM In addition CTT and its F imaging payload is internalized into PSMA expressing cells in less than minutes This irreversible binding and rapid internalization makes this molecule unique amongst PSMA inhibitors that are in development and allows for excellent biodistribution and tumor uptake In addition we are pursuing the more sensitive and quantitative diagnostic imaging modality of PET as opposed to SPECT using a F labeled radiotracer In this grant we will advance the development of our PET imaging agent CTT by completing the cGMP manufacture and automated radiolabeling of Phase I clinical material in Aim In Aim we will establish a human safety profile as well as visualize PCa lesions and determine optimal imaging parameters and dosimetry in a Phase I clinical trial in PCa patients PET imaging using our F labeled PSMA inhibitor CTT will allow for rapid and sensitive assessment of proximal and distal manifestations of PCa something which is currently unavailable PUBLIC HEALTH RELEVANCE Prostate cancer is the most frequently diagnosed malignancy in men in the US and is the second leading cause of cancer related death in men The current standard of diagnosis the PSA test correlates poorly with disease progression and treatment outcomes New and exciting treatments are emerging for metastatic prostate cancer yet because of our current dependence on the PSA test it is not clear when it is best to prescribe these treatments The overall goal of this project is to further the manufacturing and clinical development of a non invasive PET diagnostic product that can be imaged within a few hours and is expected to specifically and sensitively image both the location and extent of both early cancer escaped from the prostate as well as distal metastatic cancer including bone metastases something that all current urine serum markers and current MRI and CT scans are unable to do In addition this PET imaging agent will help determine the need for certain treatments avoiding unnecessary exposure to detrimental side effects and will effectively monitor and modify treatment regimens to achieve maximal efficacy