Synthesis and biodistribution studies of two novel radioiodinated areno-annelated estra-1,3,5(10), 16-tetraene-3-ols as promising estrogen receptor radioligands

M. C. Oliveira, M. Videira, A. Almeida, L. Gano, M. Watanabe, T. Thiemann, A. C. Santos, F. Botelho, C. Oliveira

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Two novel radioiodinated areno-annelated estra-1,3,5(10),16-tetraenes, [125I]2-iodo-1′-methoxybenzo[4′,3′:16,17]estra-1,3, 5(10),16-tetraene-3-ol (2-[125I]-MEBE) and [125I]4-iodo- 1′-methoxybenzo[4′,3′: 16,17]estra-1,3,5(10),16-tetraene-3-ol, (4-[125I]-MEBE) were synthesized for evaluation as potential ligands for the estrogen receptor. Radioiodination of 1′-methoxybenzo[4′, 3′:16,17]estra-1,3,5(10),16-tetraene-3-ol at the A ring was accomplished by electrophilic aromatic substitution using [125I] sodium iodide and chloramine-T as oxidant. After purification by reverse phase HPLC, the two radioisomers (2-[125I]-MEBE and 4-[125I]-MEBE) were obtained in a radiochemical yield of 42 and 48%, respectively, in a radiochemical purity of greater than 95% and a high specific activity. The effect of the site of radioiodination (C2 vs C4) on the biological behaviour of the molecules was evaluated through biodistribution studies in immature female Sprague-Dawley rats. Both 2-[125I]-MEBE and 4-[125I]-MEBE are stable in vivo and are mainly excreted through the hepatobiliary pathway. Both localize in the uterus and ovaries via a receptor-mediated process, where the 2-[125I]-MEBE isomer has the higher specific ER binding and uterus selectivity. The favourable in vitro/in vivo stability and biodistribution profiles suggest that these radioligands are good candidates for further exploration of their potential clinical application.

Original languageEnglish
Pages (from-to)559-569
Number of pages11
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume49
Issue number6
DOIs
Publication statusPublished - May 2006
Externally publishedYes

Keywords

  • Breast tumour imaging
  • Estradiol derivatives
  • Estrogen receptor
  • Radioiodination

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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