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First published online May 15, 2008, 10.2967/jnumed.107.048926
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Journal of Nuclear Medicine Vol. 49 No. 6 987-994
© 2008 by Society of Nuclear Medicine
doi: 10.2967/jnumed.107.048926

Basic Science Investigation

7{alpha}-18F-Fluoromethyl-Dihydrotestosterone and 7{alpha}-18F-Fluoromethyl-Nortestosterone: Ligands to Determine the Role of Sex Hormone–Binding Globulin for Steroidal Radiopharmaceuticals

Ephraim E. Parent1, Carmen S. Dence2, Terry L. Sharp2, Michael J. Welch2 and John A. Katzenellenbogen1

1 Department of Chemistry, University of Illinois, Urbana, Illinois; and 2 Washington University School of Medicine, St. Louis, Missouri

Correspondence: For correspondence or reprints contact: John A. Katzenellenbogen, Department of Chemistry, University of Illinois, 600 S. Mathews Ave., Urbana, IL 61801. E-mail: jkatzene{at}uiuc.edu

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: 7{alpha}-18F-fluoromethyl-dihydrotestosterone (7{alpha}-18F-FM-DHT) and 7{alpha}-18F-fluoromethyl-nortestosterone (7{alpha}-18F-FM-norT). Both 7{alpha}-18F-FM-DHT and 7{alpha}-18F-FM-norT have high affinity for the androgen receptor (AR); however, 7{alpha}-18F-FM-DHT has a high affinity for SHBG, whereas 7{alpha}-18F-FM-norT has a relatively low affinity. Methods: We developed an efficient radiochemical synthesis for both 7{alpha}-18F-FM-DHT and 7{alpha}-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 7{alpha}-18F-FM-DHT and 7{alpha}-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 7{alpha}-18F-FM-DHT and 7{alpha}-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.

Key Words: PET • 18F • prostate cancer • androgen receptor • sex hormone–binding globulin

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.


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