Nucl. Med. Biol. Vol. 18, No. 7, pp. 769-775, 1991 ht. .I. Rod&. A&. Instrum. Part B Printed in Great Britain. All rights reserved 0883-2897/91 $3.00 + 0.00 Copyright 0 1991 Pergamon Press plc Synthesis, Purification and Stability of No Carrier Added Radioiodinated 1,l -bis(4-Hydroxyphenyl)-2-iodo-2- phenylethylene (IBHPE), a Prototype Triphenylethylene Estrogen-receptor Binding Radiopharmaceutical S. J. GATLEY’*, E. R. DESOMBRE’, R. C. MEASE’t, R. E. SEEVERS4, A. HUGHES2. J. LI’ and M.-L. PAN’ ‘Department of Radiology and *Ben May Institute, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, ‘Department of Chemistry, Argonne National Laboratory, Argonne, IL 60439 and 4Department of Radiology, Michael Reese Hospital, Chicago, IL 60616, U.S.A. (Received 21 November 1990) A triphenylethylene compound [l ,I-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene; IBHPE] has been labeled by halodestannylation with I’3 I at a specific radioactivity of 13,200 Ci/mmol (by in vitro receptor assay) after HPLC purification. The corresponding &Br-labeled compound (BrBHPE), which has a 3-fold higher affinity for the estrogen receptor, was previously prepared and examined as a potential therapeutic radiopharmaceutical exploiting Auger electron toxicity. Stability of IBHPE was a concern because free iodide was generated when HPLC solvents were removed with a stream of nitrogen in a glass vial; however, decomposition was minimal when polypropylene vials were used, and ethanol solutions of [‘231]IBHPE were stable for several davs at 0-4°C. Tissue distribution studies of IBHPE after intra- periioneal injection to mature female rats showed highest estradiol-inhibitable uptake in the peritoneal estrogen-receptor rich tissues (uterus, ovaries and vagina) at 30min. Specific uptake (percent dose Per gram) in the pituitary, and peritoneal target tissue-to-blood ratios were greater at 2 h than 30 min. In immature female rats, uterus-to-blood ratios of >50, progressively lowered by increasing diethyl- stilbestrol levels, were obtained. These data demonstrate good binding of IBHPE to the estrogen receptor in vivo, in spite of extensive non specific binding in in vifro estrogen receptor assays. Most of the label in the uterus at 1 h after injection was still unchanged IBHPE. Our results suggest that IBHPE or related 1Z31-labeled iodovinyl triphenylethylenes could have diagnostic or therapeutic radiopharmaceutical utility. Introduction emitting nuciides may also be useful for selective Several y-ray emitting halogenated compounds which radiotherapy of ER+ neoplasms (Bloomer et al., bind to the estrogen receptor (ER) in uioo have been 1980; Bronzert et al., 1982; Jordan, 1984; Seevers, described (Gatley et al., 1981; Gibson et al., 1982; 1987). The special toxicity of Auger electron emitters Hanson er al., 1982; Hochberg, 1979; Jagoda et al., decaying near DNA, which has been well established 1984; Katzenellenbogen et al., 1981, 1982). One for 5-halodeoxyuridines (Kassis et al., 1982, 1987) rationale for preparing and investigating these com- has been demonstrated in isolated cells for “‘I- pounds is their potential for use in imaging ER+ labeled ER binding compounds (Bloomer et al., 1980; primary tumors and their metastases. Since steroid Bronzert et al., 1982). However, ‘*‘I has a physical hormone receptors are intimately associated with half-life of 60 days, and in these experiments cells DNA, ER ligands which incorporate Auger electron was stored frozen so that a lethal number of decays could accumulate. This is clearlv not nossible for the _ Present addresses: *Chemistry and tMedica1 Departments, treatment of human cancer, so that i251 compounds Brookhaven National Laboratory. Upton, NY 11973, would not be clinically useful; however, the use of a U.S.A. short-lived Auger electron emitting halogen such as 769