This project will focus on developing a radionuclide molecular imaging agent for prostate cancer that targets the prostate-specific-antigen (PSA) protease on the prostate cancer cell membrane. Following the synthesis of a fluorescently labeled molecular probe designed to specifically localize in cells expressing PSA (PSA-positive cells), the probe's targeting ability and cleaving kinetics will be assessed with in-vitro assays using PSA-positive and PSA-negative human prostate cancer cell lines. The molecular probe will then be radiolabeled. PSA-positive and PSA-negative human prostate cancer xenograft mouse models will be used to investigate the molecular probe's biodistribution. Successful in-vitro, biodistribution, and pharmacologic studies will lead to in-vivo single photon emission computed tomographic (SPECT) imaging studies in which the prostate cancer targeting ability of the radiolabeled molecular probe will be compared to that of a radiolabeled anti-PSA antibody, In addition, the ability to quantify viable tumor volume and PSA-protease expression of prostate cancers in-vivo will be evaluated using the radiolabeled molecular probe in conjunction with SPECT imaging. The long-term objective of this molecular probe development is to provide an improved approach to prostate cancer imaging which will allow more accurate prostate cancer staging. The successful implementation of the proposed targeting strategy in prostate cancer imaging will provide a foundation for the development of protease - targeting radiolabeled molecular probes for other types of cancer. This new class of radiolabeled molecular probes will have utility in cancer imaging and combined therapeutic/imaging applications. In summary, the targeting strategy developed in this project aims to open the door to novel cancer targets for nuclear imaging.
