Radiolabeling of Paclitaxel with Electrophilic 123 I Eun Joo Roh, a,d Young Hoon Park, a Choong Eui Song, a, * Seung-Jun Oh, b Yearn Seong Choe, b, * Byung-Tae Kim, b Dae Yoon Chi c, * and Deukjoon Kim d a Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, 130-650, South Korea b Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, South Korea c Department of Chemistry, Inha University, 253 Yonghyun-Dong, Nam-Ku, In-Chon, 402-751, South Korea d College of Pharmacy, Seoul National University, Shinrim-Dong, Kwanak-ku, Seoul, 151-742, South Korea Received 19 July 1999; accepted 25 August 1999 AbstractÐ 123 I-Labeled paclitaxel, [ 123 I]-1 was prepared by electrophilic aromatic radioiodination of 3 0 -N-(p-trimethylstannyl- benzoyl)-3 0 -debenzoylpaclitaxel 2 with 123 I  in the presence of peracetic acid. # 2000 Elsevier Science Ltd. All rights reserved. Introduction Paclitaxel (Taxol 1 ), a highly functionalized diterpene natural product isolated from the bark of Paci®c yew (Taxus brevifolia) demonstrated anticancer activity in human malignancies such as ovarian, breast, lung, head and neck and gastrointestinal tract cancers. 1 A unique mechanism of paclitaxel as an antimitotic agent is based on its interaction with microtubule polymers which results in the formation of stable bundles of cellular microtubules that are resistant to depolymerization back to tubulin. 2±6 Many of the paclitaxel derivatives have been evaluated in microtubule assembly assays and cytotoxicity assays against cancer cell lines. 7 Among them, analogues bear- ing a halogen substituent at the para-position of 3 0 -N- benzoyl group exhibited the ability to induce micro- tubule formation similar to that of paclitaxel. 8 From the strong microtubule binding anity and antitumor activity against lung and ovarian cancers of 3 0 -N-(p- halo-benzoyl)-3 0 -debenzoylpaclitaxel, the 3 0 -N-(p-[ 123 I]- iodobenzoyl)-3 0 -debenzoylpaclitaxel [ 123 I]-1 was designed as a cancer diagnostic radiopharmaceutical for SPECT (single photon emission computed tomography). In this paper, we report the synthesis of 3 0 -N-(p- [ 123 I]iodobenzoyl)-3 0 -debenzoylpaclitaxel [ 123 I]-1 from the trimethyltin precursor 2. Results and Discussion Synthesis of trimethyltin precursor 2 Trimethyltin precursor 2 and authentic iodopaclitaxel 1 were prepared as shown in Scheme 1. Mixed anhydride 5 was prepared by the reaction of pivaloyl chloride and p-trimethylstannylbenzoic acid in the presence of NEt 3 in CH 2 Cl 2 . p-Trimethyl- stannylbenzoic acid 4 was prepared by the reaction of ethyl p-bromobenzoate and hexamethylditin in the pre- sence of catalytic amounts of tetrakis(triphenylpho- sphine)palladium(0) in xylene, followed by hydrolysis with LiOH according to the known procedure. 9 The coupling of mixed anhydride 5 with 3 0 -amino-7-tri- chloroacetylpaclitaxel derivative 7 which was prepared 0968-0896/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0968-0896(99)00255-2 Bioorganic & Medicinal Chemistry 8 (2000) 65±68 Keywords: 3 0 -N-(p-trimethylstannylbenzoyl)-3 0 -debenzoylpaclitaxel; electrophilic aromatic radioiodination; 3 0 -N-(p-[ 123 I]iodobenzoyl)-3 0 - debenzoylpaclitaxel; SPECT (single photon emission computed tomo- graphy). *Corresponding author. Tel.: +82-2-958-5143; fax: +82-2-958-5189; e-mail: s1673@kist.re.kr