Synthesis and biodistribution studies of two novel radiolabeled estrone derivatives

Enginar H., Unak P. , Lambrecht F. , Muftuler F. Z. B. , Medine E. I.

IN VIVO, vol.22, no.1, pp.93-100, 2008 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 22 Issue: 1
  • Publication Date: 2008
  • Title of Journal : IN VIVO
  • Page Numbers: pp.93-100


Background: Two Tc-99m-DTPA attached estrone derivatives were synthesized and their radiopharmaceutical potential was determined using female albino Wistar rats. Materials and Methods: Two novel radiolabeled estrone derivatives, Tc-99m-2,2',2 '',2'''-(2,2-(2-(3-methoxy-13-methyl-17-oxo- 7, 8, 9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-2-ylamino)-2-oxoethylazanediyl) bis(ethane-2,1-diyl))bis(azanettiyl) tetraacetic acid (Tc-99m-2-DTPA-3-methoxy estrone) and Tc-99m-2,2',2 '',2'''-(2,2'-(2-(3-methoxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro- 6H-cyclopenta[a]phenanthren-4-ylamino)-2-oxoethylazanediyl) bis(ethane-2,1-dlyl))bis(azanettiyl)tetraacetic acid (Tc-99m-4DTPA-3-methoxy estrone) were synthesized starting from estrone (3-hydroxy-13-methyl-7,8, 9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one) and DTPA anhydride (2-(bis(2-(2,6-dioxomorpholino)ethyl)amino)acetic acid) as potential estrogen receptor imaging agents. The products were crystallized in ethyl alcohol (95%), purified by high performance liquid chromatography (HPLC) and characterized by nuclear magnetic resonance (NMR) and infrared spectroscopy (IR). The effect of the radiolabeled compounds on the biological behaviour of the molecules was evaluated through biodistribution studies in female albino Wistar rats. The rats were sacrificed at various time intervals, their organs were removed, and the activities of organs were counted using a gamma counter equipped with a Cd(Te) solid state detector. Results and Conclusion: Organ uptake was calculated as activity/gram tissue and time versus activity curves were generated. The tissue distribution studies exhibited a receptor-mediated uptake in the target organs of the rats for each compound. Both Tc-99m-2-DTPA-3-methoxy estrone and (99m)Tc4-DTPA-3-methoxy estrone were stable in vitro and were mainly excreted through the hepatobiliary pathway.. The biological data showed that the Tc-99m-2-DTPA-3-methoxy estrone had higher uptake in the target tissues than the Tc-99m-4-DTPA-3-methoxy estrone. The favourable in vitro/in vivo stability and biodistribution profiles suggest that these radioligands are good candidates for further exploration of their potential clinical applications.