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Radiopharmaceutcials radiolabelled with 188Re as potential therapeutic tools for hepatocellular carcinoma targeting
* 1 , 1 , 1 , 2 , 1
1  1- Université de Toulouse III, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, UMR CNRS 5068, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France
2  2- Centre Eugène Marquis, Nuclear Medicine Department, INSERM UMR-S 991, 35042, Rennes, France

Published: 02 November 2015 by MDPI in 1st International Electronic Conference on Medicinal Chemistry session ECMC-1

Hepatocellular carcinoma (HCC), is the second most common cause of death from cancer worldwide (745 000 deaths). Since 2008, HCC is the cancer with the highest mortality rate (0.95).[1] Nowadays, the only systemic treatment that has demonstrated a real benefit in advanced HCC is Sorafenib, but it remains associated with many side effects and this therapy is still very expensive. So, it is desirable to offer a treatment more efficient, and cheaper.

Many studies showed the overexpression in tumor tissue, and especially in HCC cases, of somatostatin receptors in contrast to healthy cells. [2, 3] That’s why, these kind of receptors are interesting for tumor targeting, either for imaging or for therapy. Indeed, selective localization or destruction of cancer cells by means of such radiolabelled bioconjugates is a simple and attractive concept, based on the use of the recognition properties of biomolecules towards tumour cells (magic bullet concept).[4] The challenge is to develop radiotracers, so-called radiopharmaceuticals, which consist in a three-parts system including a biomolecule, a bifunctional chelating agent (BCA) and a radioactive isotope which delivers γ or β- emission. To be efficient, this system must be stable in vivo in order to image and/or irradiate selectively the targeted tumour mass. Consequently, our challenge is to develop a targeting radiopharmaceutical with Rhenium-188 as destructive part, a tripodal N2O bifunctional chelator and as biovector, a synthetic somatostatin analogue.


In this communication, we reported our first results related to the development of a targeting radiopharmaceutical including: (i) the synthesis of original tripodal N2O BCAs based on a triazolyl moiety, these chelators being synthesised via a click chemistry approach [5], (ii) a complete structural study of corresponding non-radioactive tricarbonylrhenium complexes (iii) the first trials of coupling and of 188Re-labelling of the tripodal ligand (proof of concept).







[1]            J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D.M. Parkin, D. Forman, F. Bray, Int. J. Cancer, 2014, 136, E359–E386

[2]               J. C. Reubi, A. Zimmermann, S. Jonas, B. Waser, P. Neuhaus, U. Läderach, B. Widenmann, Gut, 1999, 45, 766-774

[3]            H. Reynaert, K. Rombouts, A. Vandermonde, D. Urbain, U. Kumar, P. Bioulac-Sage, M. Pinzani, J. Rosenbaum, A. Geerts, Gut, 2004, 53, 1180-1189

[4]            C.F. Ramogida, C. Orvig, Chem. Commun., 2013, 49, 4720-4739

[5]            S. Guizani, N. Malek-Saied, C. Picard, E. Benoist, M. Saidi, J. Label. Compd Radiopharm., 2014, 57, 158-163.

Keywords: Rhenium, Bifunctional chelating agent, Radiopharmaceuticals, Click chemistry