Preparation and preliminary bioevaluation of 99mTc(CO)3-11β-progesterone derivative prepared via click chemistry route

Introduction: Progesterone receptors (PRs) overexpressed in breast cancers serve as potential targets for developing radiotracers for use in nuclear medicine. Hence, suitably derivatized progesterone can be envisaged as a potential vector for targeting overexpression of receptors in breast cancer. In the present article, we report the preparation of a Tc-99m(CO)(3)-progesterone triazole using the Cu(I)-catalyzed novel click chemistry route. Preliminary evaluation of the radiolabeled derivative has been carried out in binding studies with MCF7 cell lines. Methods: 11-Hydroxyprogesterone has been synthetically derivatized to 11-azidoprogesterone. Subsequently, the cycloaddition reaction between progesterone azide and propargyl glycine was carried out to prepare 1,4-bifunctionalized progesterone triazole analogue. The clicked progesterone triazole derivative was radiolabeled with Tc-99m and characterized by HPLC. The chemical characterization of Tc-99m(CO)(3)-progesterone triazole has been carried out by preparing its corresponding rhenium complex using the [NEt4](2)[Re(CO)(3)Br-3] precursor. While in vitro studies were carried out in MCF7 cell lines, in vivo distribution studies were performed in female Swiss mice. Results: The radiolabeled complex could be prepared in >95% radiochemical yield as determined by HPLC. In vitro studies of Tc-99m(CO)(3)-progesterone complex in MCF7 cell lines overexpressing receptors for breast cancer showed binding up to 30%. In vivo distribution studies in female Swiss mice have shown uterine uptake of 0.41 (0.06) % ID/g at 3 h postinjection (pi) and retention therein till 24 h pi. Conclusion: The present study demonstrates a novel and facile route for preparation of Tc-99m-labeled progesterone complex using click chemistry. This strategy can be further extended towards preparation of radiolabeled complexes of other steroidal derivatives. (C) 2010 Elsevier Inc. All rights reserved.