Synthesis of an estradiol glucuronide derivative and investigation of its radiopharmaceutical potential

Biber F. Z., ÜNAK P., Ertay T., Medine E. I., ZİHNİOĞLU F., Tasci C., ...More

APPLIED RADIATION AND ISOTOPES, vol.64, no.7, pp.778-788, 2006 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 64 Issue: 7
  • Publication Date: 2006
  • Doi Number: 10.1016/j.apradiso.2006.02.001
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.778-788
  • Keywords: estradiol derivative radiopharmaceuticals, beta-estradiol (1,3,5,[10]-estratrien-3,17 beta-diol), DTPA, Tc-99m-ESTDTPA, Tc-99m-ESTDTPAG, 7,12-dimethylbenzantracene (DMBA), BLOOD-BRAIN-BARRIER, BETA-D-GLUCURONIDE, ESTROGENS, BIODISTRIBUTION, PERMEABILITY, OPTIMIZATION, TC-99M, CANCER
  • Dokuz Eylül University Affiliated: Yes


The aim of the current study was to synthesize a derivative of estradiol glucuronide, which is able to be labeled with Tc-99m and to investigate its radiopharmaceutical potential using imaging and biodistribution studies. An estrogen derivative, beta-estradiol (1,3,5,[10]estratriene-3,17 beta-diol) attached to diethylenetriamine pentaacetic acid (DTPA) was synthesized in six steps. At the end of these steps a compound of estradiol and DTPA derivative called deoxy demethyl homoestradiolyl diethylenetriamine pentaacetic acid (ESTDTPA) was synthesized. Afterwards, this compound was reacted with UDP-glucuronyl transferase (UDPGT). Following the glucuronidation reaction, the product called deoxy demethyl homoestradiolyl diethylenetriamine pentaaceticacid-glucuronide (ESTDTPAG) was obtained. Synthesized products were purified using high performance liquid chromatography (HPLC). The identification of the purified products and impurities were also established using HPLC. Synthesized compound was labeled with Tc-99m. Thin layer radio chromatography (TLRC) technique was used to determine their radiochemical yields and stabilities. Labeling yield was over 96%. The biodistribution studies were performed on female Albino Wistar rats. The activity per gram tissue was calculated and time-activity curves were plotted. The target organs (tumor, as well as uterus, ovaries, adrenals and other ER containing tissues) retain the estradiol derivative longer than nontarget organs, but even these lost most of their activity within a few hours.