7α-Methy-17α-(E-2′[ 125l]iodvinyl)-19-nortestosterone: A new radioligand for the detection of androgen receptor

Article abstract of DOI:10.1016/0039-128X(93)90012-C

We have synthesized two γ-emitting, ¹²⁵I-labeled steroids, E- and Z-7α-methyl-17α-((2′-[ ¹²⁵I]iodovinyl)-19-nortestosterone [¹²⁵I](E- and Z-MIVNT) for specific labeling of androgen receptors. [¹²⁵I]E- and [¹²⁵I]Z-MIVNTwere synthesized stereospecifically from E- and Z-7α-methyl- 17α-(2′-tri-n-butylstannylvinyl)-19-nortestosterone. The tin adducts were prepared by addition of tri-n-butyltin hydride to 7α-methyl-17α-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-labeledproducts 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 5α-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 (k_diss for BOTH = 0.04 h-1). Displacement studies showed that the interaction of[¹²⁵I]E-MIVNTwith 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 [¹³²⁵I]E-MIVNT a potential imaging agent for the detection of androgen-dependent tumors, such as prostate cancer. (Steroids 58:13-23, 1993).