) This year 179,300 men in US will be diagnosed with prostate carcinoma and approximately 25 percent of them will die of this disease. Current diagnostic methods including transrectal ultrasound (TRUS) and TRUS guided prostate biopsy are logically difficult and insensitive. Positron emission tomography (PET) provides an accurate and sensitive imaging method for detection of prostate cancer. The capability of PET to provide accurate quantitation of receptor density or metabolism is a fundamental advantage over other available imaging moralities. PET also permits quantification of tumor invasion and the detection of smaller metastatic lesions. We propose the detection of prostate tumors and metastases using positron emission tomography (PET) and a radiofluorinated ligand that concentrates in tumors through the action of the androgen receptor. This radiolabeled tumor probe will enable precise localization and detection of the primary tumor and metastases or surgical removal, as well for follow up on the outcome of chemotherapy and surgery. This technique will have clinical importance in aiding the physicians in planning and selecting the appropriate treatment regimen. In order to achieve our goals, Our specific aims are: To optimize the radiochemical synthesis of 7 alpha F-17 alpha-CH expo 3-5 alpha-DHT. To provide in vivo metabolic protection for 7 alpha negative 18 F negative 17 alpha-androgens. To assess the biological activity of the proposed radiotracer in vitro and in vivo. We have synthesized 7 alpha-fluoro-17(alpha-methyl-5 alpha-DHT showing excellent androgen receptor binding properties with an RBA better than the potent androgen 5 alpha-DHT. We have also synthesized 7 alpha negative expo 18 F-17 alpha-CH expo 3 negative-5 alpha-DHT in poor to modest radiochemical yields and performed in vivo distribution studies (The data are presented in Preliminary Results section) exhibiting 10/1 prostate to nonspecific tissue ratio. We plan to explore this newly developed tracer for its potential as clinically utilizable imaging agent.
