PMID- 8003436
OWN - NLM
STAT- MEDLINE
DCOM- 19940719
LR  - 20190830
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 49
IP  - 1
DP  - 1994 May
TI  - Synthesis of (17 alpha,20E/Z)iodovinyl testosterone and 19-nortestosterone 
      derivatives as potential radioligands for androgen and progesterone receptors.
PG  - 15-29
AB  - To develop androgen and progesterone receptor-based radioligands for SPECT 
      imaging we synthesized several radioiodinated 17 alpha-iodovinyl testosterone and 
      19-nortestosterone analogs and evaluated their biological properties. The 
      synthesis of these compounds proceeds via the (17 alpha,20E/Z)stannyl 
      intermediates and involves addition of tri-n-butyltin hydride to the 17 
      alpha-ethynyl group of the steroid using either azobisiso butyronitrile or 
      triethylborane as a catalyst. The stannyl derivatives are stereospecifically 
      converted to the corresponding (17 alpha,20E/Z)iodovinyl derivatives using 
      molecular iodine, or to the [125I]iodovinyl analogs using [125I]NaI and H2O2. 
      Androgen and progesterone receptor (AR and PgR) binding affinities were measured 
      via a competitive in vitro binding assay. In general 19-nortestosterone 
      derivatives showed higher receptor affinities as compared to the testosterone 
      derivatives. In the latter series the highest PgR binding affinities were 
      observed with the (17 alpha,20Z)iodovinyl-19-nortestosterone (IVNT) (92 vs 100 
      for R5020) followed by the 7 alpha-methyl analog, whereas the highest AR binding 
      affinity was observed with the 7 alpha-Me-(17 alpha,20Z)IVNT (54 vs 100 for 5 
      alpha-dihydrotestosterone). These derivatives were also labeled with 125I and 
      evaluated for their in vivo target organ uptake (prostate and estrogen-primed 
      uterus). The highest PgR-mediated target tissue uptake was observed with the (17 
      alpha,20Z)-[125I]IVNT and its 7 alpha-methyl derivatives whereas only one 
      derivative, the 7 alpha-Me-(17 alpha,20Z)-[125I]IVNT, showed AR-mediated dorsal 
      prostate retention. Although some of the IVNT derivatives have interesting 
      binding properties, the lack of in vivo selectivity does suggest that the 
      123I-labeled analogs are unlikely to be suitable for imaging of AR and PgR-rich 
      tissues.
FAU - Ali, H
AU  - Ali H
AD  - MRC Group in the Radiation Sciences, Faculty of Medicine, University of 
      Sherbrooke, Quebec, Canada.
FAU - Rousseau, A J
AU  - Rousseau AJ
FAU - van Lier, J E
AU  - van Lier JE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Receptors, Progesterone)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 3XMK78S47O (Testosterone)
RN  - 6PG9VR430D (Nandrolone)
RN  - 99608-22-7 ((2-iodovinyl)-19-nortestosterone)
SB  - IM
MH  - Animals
MH  - Dihydrotestosterone/pharmacokinetics
MH  - Female
MH  - Iodine Radioisotopes/metabolism/pharmacokinetics
MH  - Male
MH  - Nandrolone/*analogs & derivatives/chemical synthesis/metabolism/pharmacokinetics
MH  - Prostate/metabolism
MH  - Radioligand Assay/*methods
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Androgen/*metabolism
MH  - Receptors, Progesterone/*metabolism
MH  - Testosterone/*analogs & derivatives/chemical 
      synthesis/metabolism/pharmacokinetics
MH  - Thyroid Gland/metabolism
MH  - Tissue Distribution
MH  - Uterus/metabolism
EDAT- 1994/05/01 00:00
MHDA- 1994/05/01 00:01
CRDT- 1994/05/01 00:00
PHST- 1994/05/01 00:00 [pubmed]
PHST- 1994/05/01 00:01 [medline]
PHST- 1994/05/01 00:00 [entrez]
AID - 10.1016/0960-0760(94)90296-8 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1994 May;49(1):15-29. doi: 
      10.1016/0960-0760(94)90296-8.