Abstract: A method for producing a high yield of an estradiol labeled at the 16-alpha position thereof with a radioactive iodine, especially 123I, for use as an imaging agent. The method includes the step of mixing a source of 123I sodium iodine with 16-beta-bromoestradiol-17-beta and benzo-15-crown-5-ether in a water and organic solvent solution and heating under controlled temperature in the range from 90 to 120° Centigrade for sufficient time to react the iodide with the estradiol. Thereafter, resulting 16-alpha-123I iodoestradiol-17-beta is separated from the resultant mixture using high pressure liquid chromatography and then sterilized.

Abstract: A process for detecting a presence of steroid receptors in tissue therapeutically and for treating certian tissue, especially tissue having estrogen receptors, includes the step of treating the tissue by injection, surface application or the like, with a labeled steroid. The labeled steroid may include a moiety which is readily imageable on a gamma radiation detector, on x-ray film, on a fluoroscope, through NMR devices or the like. An especially suitable labeled steroid has been found to be 16-.sup.123 I-17-beta-estradiol having a specific activity of greater than 2,000 curies per millimole and preferably at least 5,000 curies per millimole.

Abstract: A method of preparation of estradiol derivatives labeled by iodine, especially .sup.123 I, substitution at C-16 are synthesized according to the present invention. A triflate intermediate is prepared from which either 16-alpha-.sup.123 I-17-beta-estradiol or 16-beta-.sup.123 I-17-beta-estradiol are prepared by described methods. Both 16-alpha-.sup.123 I- and 16-beta-.sup.123 I-17-beta-estradiol made according to the methods described herein have a high relative specific acitvity. The methods are sufficiently rapid so that the relatively short half-life of .sup.123 I is readily accommodated without substantial radioactive decay of the label.

Abstract: A method of preparation of halogen labeled organic compounds is described. In particular, estradiol derivatives labeled by halogen substitution at C-16 are synthesized according to the present invention. A triflate intermediate is prepared from which either 16-alpha-halo-substituted-17-beta-estradiols or 16-beta-halo-substituted-17-beta-estradiols can be rapidly formed as desired. In particular, the preparation of 16-alpha-.sup.123 I-17-beta-estradiol and 16-beta-.sup.123 I-17-beta-estradiol are shown and are synthesized from a 17-beta-estradiol-16-beta-triflate. Both 16-alpha-.sup.123 I- and 16-beta-.sup.123 I-17-beta-estradiol made according to the present invention are shown to have a high specific activity. The method of synthesis is sufficiently rapid so that the relatively short half-life of .sup.123 I is readily accommodated. The high stereospecificity of each step of the reaction sequence in preparing the labeled estradiols provides for highly efficient syntheses and little waste of radio-label.