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As part of our program to develop radiopharmaceuticals for the detection and diagnosis of estrogen-responsive breast cancer, we have focused on the use of organometallic substituents to facilitate the introduction of the radionuclide. As a result we initiated the application of organotin chemistry to the field of radiopharmaceutical chemistry in our preparation of the labeled antiestrogen [125I]iodotamoxifen.1-3 In that synthesis we could selectively lithiate and subsequently stannylate ortho to the (dimethylamino)ethoxy group, and electrophilic radioiododestannylation proceeded rapidly and in very high yield. We have extended this approach in the field of estrogen receptor binding agents to the synthesis of radioiodinated 17«-[5-iodothien-2-yl]1 234 5and 17a-(£)-iodovinyl estrogens.54Because of the availability of other radionuclides of potential in vitro or in vivo clinical interest, e.g., 3H, 75Br, 76Br, and 73Se, we have undertaken a preliminary examination of other electrophilic species containing these elements. This paper describes the results of this study in which a series of specifically substituted (17a,20E)-19-norpregnal,3,5(10)20-tetraene-3,17d-diols (17a-vinylestradiols) were prepared and characterized.

17a -E-Bromovinylestradiol and its radiobrominated analogs were prepared by halodestannylation.The synthesis was achieved by bromination of the tri-n-butylstannylvinyl intermediate to give a 90% isolated yield. &Jhe reaction of the intermejjate with ammonium I Br] bromide or sodium [ Brl bromide in the presence of an oxidant give the corresponding radiolabeled bromovinylestradiol in 80-90% yields after isolation by HPLC.The radiochemical purity was greater than 98% and no other UV-active compounds could be detected by HPLC.An in vivo comparison of thiq2Sompound wit!! the previously prepared 17 a -E- [ I] iodovinyl estradiol indicated that the two compounds had similar uterine uptake and specific receptor binding properties.The results suggest that radiobromodestannylation may be the method of choice for the preparation of this and other structurally similar compounds. long term survival (1-5).Because of the potential advantages associated with noninvasive in vivo detection and localization of estrogen receptor containing tumors several approaches have been undertaken to synthesize radiolabeled ligands that have a high affinity for the estrogen receptor protein (6). These ligands, labeled with gamma-or positron-emitting radionuclides, could potentially provide external visualization of the estrogen receptor containing tumors via scintigraphic imaging ( 7-17). This goal has been realized by the demonstration that 16 a -[F-18]estradiol can indeed image the estrogen receptor containing breast tumors in vivo. (18,19) In previous studies we have reported the preparation and evaluation of the radioiodinated 17a -E-iodovinylestradiol and its derivatives as potential tumor imaging agents (20-23) from which 17 a -iodovinyl-llD -methoxyestradiol demonstrated that the best uterine uptake and selectivity (17 , 22 , 24,25). Although most of the research related to radiolabeled estrogens has focused on the use of fluorine-18 and iodine-123, bromine which also has several radioisotopes has been discussed in several reviews (26,271. Bromine-75, a positron emitter (T1/2 = 101 minutes) has the greatest potential for radiodiagnostic applications, and bromine-80m, an Auger electron-emitter (T1/2 = 4 . 4 h. 1 , has potential for radiotherapy. The other radioisotopes, bromine-77 (T1/2 = 56 hr.) and bromine-82 (t1/2 = 35.3 h) have poorer clinical characteristics but are more readily produced, can be used for chemical and biological studies. This has been done previously for synthesis of several radiobrominated estrogens (12,13,28-31). With the potential incorporation of 75Br in mind, we report here our studies involving the bromination and radiobromination of 17a-tri-n-butylstannyl-vinylestradiol, 4, and a preliminary evaluation of 17a -[Br-77]bromovinylestradiol *. 1701-E-Bromovinylestradiol and its Analogs 17a-E-Bromovinylestradiol and its Analogs -J. Nucl. Med. 2:522 (1983) Landvatter S.W.,

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Zur positionsspezifischen Deuterierung und Tritiierung eignet sich die Umsetzung von Zinnverbindungen wie (I) mit Deuterium‐ bzw. Tritiumoxid (II).