| Abstract
| - Although prostate cancer growth is regulated by androgens through the androgen receptor (AR), in vitroassays of AR levels in prostate tumors have limited prognostic value. This might be improved by directmeasurement of tumor AR in vivo using positron emission tomography (PET) imaging with fluorine-18-labeled androgens. Most AR PET imaging agents have been designed to limit steroid binding toserum proteins, but there is evidence that binding to sex hormone binding globulin (SHBG) might enhancetumor uptake. To probe the role of SHBG in prostate tumor uptake of PET imaging agents, we havesynthesized two fluoro steroids, 7α-(fluoromethyl)dihydrotestosterone (7α-FM-DHT) and 7α-(fluoromethyl)nortestosterone (7α-FM-norT), by a route amenable to their labeling with [18F]fluoride ion. Bothcompounds have high affinity for AR, but 7α-FM-norT has much lower affinity for SHBG. Thus, thesetwo fluoro steroids are well matched in terms of their site of fluorine labeling, similarity of structure,and equivalent AR binding affinitybut contrasting SHBG bindingand therefore can be used as agentsfor evaluating the role of SHBG binding in the target tissue uptake of AR PET imaging agents in humans.
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