title: 7alpha-18F-fluoromethyl-dihydrotestosterone and 7alpha-18F-fluoromethyl-nortestosterone: ligands to determine the role of sex hormone-binding globulin for steroidal radiopharmaceuticals.
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: 7alpha-18F-fluoromethyl-dihydrotestosterone (7alpha-18F-FM-DHT) and 7alpha-18F-fluoromethyl-nortestosterone (7alpha-18F-FM-norT). Both 7alpha-18F-FM-DHT and 7alpha-18F-FM-norT have high affinity for the androgen receptor (AR); however, 7alpha-18F-FM-DHT has a high affinity for SHBG, whereas 7alpha-18F-FM-norT has a relatively low affinity.
  
  
  METHODS
  We developed an efficient radiochemical synthesis for both 7alpha-18F-FM-DHT and 7alpha-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 7alpha-18F-FM-DHT and 7alpha-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.
  
  
  CONCLUSIONS
  These studies show that 7alpha-18F-FM-DHT and 7alpha-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.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: Ephraim E
authors.initials: EE
authors.lastname: Parent
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Dence
authors.forename: Terry L
authors.initials: TL
authors.lastname: Sharp
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
mesh_terms: D000818:Animals; D008024:Ligands; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D008024:Ligands; D019275:Radiopharmaceuticals; D012738:Sex Hormone-Binding Globulin