PT - JOURNAL ARTICLE AU - Ephraim E. Parent AU - Carmen S. Dence AU - Terry L. Sharp AU - Michael J. Welch AU - John A. Katzenellenbogen TI - 7α-<sup>18</sup>F-Fluoromethyl-Dihydrotestosterone and 7α-<sup>18</sup>F-Fluoromethyl-Nortestosterone: Ligands to Determine the Role of Sex Hormone–Binding Globulin for Steroidal Radiopharmaceuticals AID - 10.2967/jnumed.107.048926 DP - 2008 Jun 01 TA - Journal of Nuclear Medicine PG - 987--994 VI - 49 IP - 6 4099 - http://jnm.snmjournals.org/content/49/6/987.short 4100 - http://jnm.snmjournals.org/content/49/6/987.full SO - J Nucl Med2008 Jun 01; 49 AB - 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.