7 alpha-Methyl-17 alpha-(E-2'-[125I]iodovinyl)-19-nortestosterone: a new radioligand for the detection of androgen receptor.

Abstract

We have synthesized two gamma-emitting, 125I-labeled steroids, E- and Z-7 alpha-methyl-17 alpha-(2'-[125I]iodovinyl)-19-nortestosterone [125I](E- and Z-MIVNT) for specific labeling of androgen receptors. [125I]E- and [125I]Z-MIVNT were synthesized stereospecifically from E- and Z-7 alpha-methyl-17 alpha-(2'-tri-n-butylstannyl-vinyl)-19-nortestosterone. The tin adducts were prepared by addition of tri-n-butyltin hydride to 7 alpha-methyl-17 alpha-ethynyl-19-nortestosterone, and after purification they were converted in high yield to the [125I]MIVNT isomers by reaction with 125I (generated in situ by oxidation of [125I]iodide with chloramine T). The 125I-labeled products were purified by high-performance liquid chromatography, and their mass determined with an ultraviolet detector (specific activity of both, approximately 2,200 Ci/mmol). In rat prostate cytosol, [125I]E-MIVNT bound with high affinity to a single class of binding sites. Nonspecific binding in the presence of 5 alpha-dihydrotestosterone was relatively low, and compared favorably with that obtained in parallel studies with [3H]methyltrienolone (R1881). The E-isomer bound prostate cytosol with at least twice the affinity of the Z-isomer; therefore, the interaction of the E-isomer with the androgen receptor as well as other steroid receptors was studied in greater detail. Complexes of the androgen receptor with [125I]E-MIVNT as well as [3H]R1881 dissociate very slowly at 4C (kdiss for both = 0.04 h-1). Displacement studies showed that the interaction of [125I]E-MIVNT with the androgen receptor is highly specific. Competition studies showed that unlabeled E-MIVNT binds poorly to other steroid receptors in rat tissue cytosols. These binding properties make [125I]E-MIVNT a promising ligand for study of the androgen receptor, and [123I]E-MIVNT a potential imaging agent for the detection of androgen-dependent tumors, such as prostate cancer.

• Authors: R M Hoyte, T J Brown, N J MacLusky, R B Hochberg
• Journal: Steroids (Steroids) Vol. 58 Issue 1 Pg. 13-23 (Jan 1993) ISSN: 0039-128X [Print] United States
• PMID: 8430441 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chloramines
• Iodine Radioisotopes
• Receptors, Androgen
• Tosyl Compounds
• Trialkyltin Compounds
• chloramine-T
• 7-methyl-17-(2'-iodovinyl)-19-nortestosterone
• Metribolone
• tributyltin
• Nandrolone

Topics

• Animals
• Binding, Competitive
• Chloramines
• Drug Stability
• Female
• Iodine Radioisotopes
• Isotope Labeling
• Kinetics
• Liver (metabolism)
• Male
• Metribolone (metabolism)
• Nandrolone (analogs & derivatives, chemical synthesis, chemistry, metabolism)
• Oxidation-Reduction
• Prostate (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Androgen (metabolism)
• Tosyl Compounds
• Trialkyltin Compounds
• Uterus (metabolism)