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

Journal of Nuclear Medicine

Terry L. Sharp¹  Ephraim E. Parent¹  Carmen S. Dence¹  Michael J. Welch¹  John A. Katzenellenbogen¹ 

关键词: PET;    ¹⁸F;    prostate cancer;    androgen receptor;    sex hormone–binding globulin;   

DOI  :  10.2967/jnumed.107.048926

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown