Book of Abstracts - Ruhr-Universität Bochum

P-54
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Synthesis and Biological evaluation of [99mTc]-N-[4-nitro-3-trifluoromethylphenyl]
Cyclopentadienyltricarbonyltechnetium Carboxamide, a Nonsteroidal
Antiandrogen Flutamide Derivative
Tensim Dallagi, a S. Top, b S. Masi, b G. Jaouen, b and M. Saidi a
a Unité d'utilisation Médicale et Agricole des Techniques Nucléaires Laboratoire des
Radiopharmaceutiques, Centre National des Sciences et Technologies Nucléaires,
Technopôle de Sidi Thabet, 2020 Sidi Thabet,Tunisie. E-mail : t.dallegi@laposte.net. b Ecole
Nationale Supérieure de Chimie de Paris, Laboratoire Charles Friedel, UMR 7223, 11, rue Pierre et
Marie Curie, F-75231 Paris Cedex 05, France. E-mail : siden-top@chimie-paristech.fr
Prostate cancer is one of the most frequently diagnosed cancers and is the second leading cause of
cancer death in American men, after lung cancer. 1 In 2009, prostate cancer is predicted to kill 27,360
American men. A similar statistic holds for French men. It is important to note that when the cancer is
detected it has already had a long time to develop. Therefore, it is crucial to detect the cancer at its
earliest stages. Few compounds have been labelled with 99m Tc for use as androgen receptor-based
prostatic imaging agents. 2,3 Rapid metabolic cleavage, low receptor binding affinity or inadequate
specific activity is a common feature of most of PET and SPECT radioimaging agents. We have
recently developed ferrocenyl derivatives of nonsteroidal antiandrogens and have found that
ferrocenyl nilutamide derivatives show a significant cytotoxicity on hormone-independent prostate
cancer cells PC-3. 4
O2N O
O2N O
F3C N
H
F3C N
Fe
H
NFFe
112
NF 99m Tc
NFRe
99m Tc(CO)3
(M = 99m Tc)
(M = Re)
In our efforts to develop a novel class of SPECT imaging agents based on nonsteroidal androgen
receptor (AR) antagonists, we have synthesized N-cyclopentadienyltricarbonyltechnetium-N-[4-nitro-
3-trifluoromethyl-phenyl] carboxamide (NF 99m Tc), an analog of the AR antagonist ligand flutamide.
NF 99m Tc was obtained in 82% yield from the reaction of N-[4-nitro-3-trifluoromethyl-phenyl]ferrocenecarboxamide
(NFFe) with fac-[ 99m Tc(H2O)3(CO)3] + in DMF/water at pH 1 and at 150 °C for
1 h. We also prepared N-[4-nitro-3-trifluoromethyl-phenyl]-rheniumcyclopentadienyltricarbonylcarboxamide
(NFRe) which is useful for the identification of the technetium compound. In vitro
assays demonstrated high stability of NF 99m Tc under physiological conditions, buffer and blood. The
tissue biodistribution in mature male Wistar rats showed a significant selective uptake by prostate but
this uptake was not blocked by an excess of testosterone acetate.
References
1. A. Jemal, R. Siegl, E. Ward, Y. Hao, J. Xu, M. J. Thun, CA Cancer J. Clin. 2009, 59, 225-249.
2. T. Das, S. Banerjee, G. Samuel, K. Bapat, S. Subramanian, M. R. A. Pillai, M. Venkatesh, Bioorg.
Med. Chem. Lett., 2006, 16, 5788-5792.
3 H. He, J. E. Morely, E. Silva-Lopez, B. Bottenus, M. Montajano, G. A. Fugate, B. Twamley, P. D.
Benny, Bioconjugate Chem. 2009, 20, 78-86.
4. O. Payen, S. Top, A. Vessières, E. Brulé, M.-A. Plamont, M. J. McGlinchey, H. Müller-Bunz, G.
Jaouen, J. Med. Chem. 2008, 51, 1791-1799.