Prostate cancer represents a significant health problem in the United States. This year 179,000 men in the US will be diagnosed with prostate carcinoma and approximately 25% of them will die of this disease. This laboratory has successfully synthesized an F-18 labeled androgen, 7alpha-18F-17alpha-methyl-5adihydrotestosterone ([18F]FMDHT) that would be suitable for imaging prostate tumors. This proposal explores the potential of [18F]FMDHT in vivo using androgen receptor positive tumor xenograft in athymic mouse model. Subsequently, we will utilize micro-PET imaging methods to assess specificity and selectivity of [18F]FMDHT in rodent tumor xenograft model, PET imaging in non-human primates to optimize the imaging characteristics. If successful, this proposal will present us with a radiotracer to diagnose prostate cancer with high specificity and selectivity. In order to achieve our goals, our specific aims are:
Specific Aim 1 : Evaluate tissue distribution of [18F]FMDHT in chemically castrated rats and in castrated rabbits using biodistribution and microPET imaging studies;
Specific Aim 2 : Assess selectivity of tracer uptake in tumor and normal tissue in a tumor xenograft model of athymic mice using biodistribution and microPET imaging studies.
Specific Aim 3 : Perform microPET imaging studies to assess specificity of tracer using pharmacological intervention studies in rodents Specific Aim 4: Perform PET imaging studies to assess imaging characteristics and obtain radiation dose estimates for humans using non-human primate model. To this end, we have synthesized [18F]FMDHT. Tissue distribution studies using rats show specific to non specific ratio of approximately 15. Androgen receptor rich ventricle lobes of prostate were clearly visualized on Micro-PET images. Tumor could be visualized on microPET images using LnCAP tumor xenograft in mice. We propose to assess its potential as clinically viable tumor imaging agent utilizing more robust experimental models. Our major goal is to develop an androgen receptor avid PET probe to image prostate cancer. If successful, this diagnostic probe will enable precise localization and detection of the primary tumor and metastases for surgical removal, as well for follow up of outcome of chemotherapy and surgery. This technique would also aid clinicians in planning and selecting the appropriate treatment regimen.
