Positron tomographic assessment of androgen receptors in prostatic carcinoma.
OBJECTIVE
The purpose of this study was to evaluate the feasibility of androgen receptor (AR) imaging with 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT) by positron emission tomography (PET) and to assess the binding selectivity of FDHT to AR in patients with prostate cancer.


METHODS
Twenty men (age range 56-87 years) with advanced prostate cancer were studied. All except one had metastatic disease confirmed by biopsy and/or radiological studies. One patient who had radiological findings suggesting a single hepatic metastasis was found to have focal fatty infiltration on biopsy obtained after FDHT-PET and was excluded from further data analysis. FDHT uptake was assessed semiquantitatively by determination of the standardized uptake value (SUV) and tumor-to-muscle ratio (T/M). Additionally, to assess the AR binding selectivity of FDHT, patients with one or more foci of abnormally increased FDHT accumulation were studied after administration of an AR antagonist (flutamide).


RESULTS
Conventional imaging demonstrated innumerable lesions in two patients and 43 lesions in the remaining 17 patients with advanced prostate cancer. FDHT-PET was positive in 12 of 19 patients (sensitivity of 63%), including the two patients with innumerable lesions. FDHT-PET detected 24 of 28 known lesions (86%) in the remaining ten patients. In addition, FDHT-PET detected 17 unsuspected lesions in five of these ten patients. All 12 patients with positive FDHT-PET underwent a repeat PET study after receiving flutamide for 1 day (250 mg t.i.d.). In all of these patients, there was a decrease in tumor FDHT uptake after flutamide; the mean (+/- standard deviation) SUV and T/M decreased from 7.0+/-4.7 and 6.9+/-3.9, respectively, to 3.0+/-1.5 and 3.0+/-1.6, respectively (p=0.002). The mean PSA in patients with positive FDHT-PET was significantly higher than that in patients with negative FDHT-PET (p=0.006).


CONCLUSIONS
Our results document the feasibility of PET imaging of prostate cancer with FDHT and suggest that tumor uptake of FDHT is a receptor-mediated process. Positive PET studies were associated with higher PSA levels and thus, presumably, with greater tumor burden.
Dehdashti
Farrokh
F
The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 63110, USA. dehdashtif@mir.wustl.edu
Picus
Joel
J
Michalski
Jeff M
JM
Dence
Carmen S
CS
Siegel
Barry A
BA
Katzenellenbogen
John A
JA
Welch
Michael J
MJ
D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011467:Prostate / Q000000981:diagnostic imaging / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*
C494901:16-fluorodihydrotestosterone; D005462:Fluorine Radioisotopes; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D017430:Prostate-Specific Antigen
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