7α-18F-fluoromethyl-dihydrotestosterone and 7α- 18F-fluoromethyl-nortestosterone: Ligands to determine the role of sex hormone-binding globulin for steroidal radiopharmaceuticals

Ephraim E. Parent, Carmen S. Dence, Terry L. Sharp, Michael J. Welch, John A. Katzenellenbogen

Research output: Contribution to journalArticlepeer-review

Abstract

Sex hormone-binding globulin (SHBG) is believed to play a key role in steroidal radiopharmaceutical delivery to target tissues in humans. To better understand the action of SHBG, we have synthesized and tested in vivo 2 novel 18F-labeled androgens: 7α-18F-fluoromethyl- dihydrotestosterone (7α-18F-FM-DHT) and 7α- 18F-fluoromethyl-nortestosterone (7α-18F-FM-norT). Both 7α-18F-FM-DHT and 7α-18F-FM-norT have high affinity for the androgen receptor (AR); however, 7α- 18F-FM-DHT has a high affinity for SHBG, whereas 7α- 18F-FM-norT has a relatively low affinity. Methods: We developed an efficient radiochemical synthesis for both 7α-18F-FM-DHT and 7α-18F-FM-norT, producing them in good radiochemical yield and high specific activity. Biodistribution studies of both compounds were done on diethylstilbestrol-pretreated and DHT-blocked Sprague-Dawley male rats. Metabolism studies were done to determine the amount of intact ligand in the prostate. Results: We obtained 7α-18F-FM-DHT and 7α- 18F-FM-norT in radiochemical yields of about 30% and radiochemical purities of greater than 99%. Rat biodistribution studies showed selective AR-mediated uptake in the prostate for both compounds. Both compounds showed relatively little defluorination, but the norT analog was more metabolically stable than the DHT analog. Conclusion: These studies show that 7α- 18F-FM-DHT and 7α-18F-FM-norT have potential for use in human clinical imaging trials to evaluate more definitively the role of SHBG in radiotracer delivery of steroidal systems to target tissues.

Original languageEnglish (US)
Pages (from-to)987-994
Number of pages8
JournalJournal of Nuclear Medicine
Volume49
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • F
  • Androgen receptor
  • PET
  • Prostate cancer
  • Sex hormone-binding globulin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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