Positron tomographic assessment of androgen receptors in prostatic carcinoma

Farrokh Dehdashti, Joel Picus, Jeff M. Michalski, Carmen S. Dence, Barry A. Siegel, John A. Katzenellenbogen, Michael J. Welch

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

Purpose: The purpose of this study was to evaluate the feasibility of androgen receptor (AR) imaging with 16β-[18F]fluoro-5α- 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)344-350
Number of pages7
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume32
Issue number3
DOIs
StatePublished - Mar 1 2005

Keywords

  • Androgen
  • Cancer
  • PET
  • Prosteate
  • Receptor

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