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Nouvel Agent anticancéreux

23/03/2017
Nous avons contribué avec l'équipe du Pr Yang du CHU de Tangji (Shanghai , Chine) à la mise au point d'un nouvel agent anticancéreux issu de la nanotechnologie. Ces travaux ont été publiés dans la revue scientifique Drug Designing: Open Access.

Research Article

New Potential In Situ Anticancer Agent Derived from [188Re]rhenium Nitro-Imidazole Ligand Loaded 5th Generation Poly-L-Lysine Dendrimer for Treatment of Transplanted Human Liver Carcinoma in Nude Mice

Yang Guanghua, Sadeg Nouredine and Hafid Belhadj-Tahar
1- Nanomedicine Research and Expertise Group, French Association for Medical Research Advancement, (AFPREMED-Canceropole), France
2- Research Center for Translational Medicine, East Hospital, School of Medicine, Tongji University, Shanghai 200120, China



Drug Designing 2017 , 6 (1):1-7


To read the full article Peer-reviewed Article PDF [3 112 KB]

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and one of the fifth most common tumors worldwide. In this article we report the results of in vivo studies of potential anticancer agent "[188Re] rhenium-ImDendrim" derived from [188Re]rhenium-nitro-imidazole-methyl -1,2,3-triazol-methyl-di-(2-pycolyl)amine as radioactive ligand loaded 5th generation poly-L-lysine denrimer (172,3 kDa, 20 nM). Methods: 5.0 × 10 E6 cells were subcutaneously injected into mice. Once tumor established, 4 mice lots were treated with a single dose of the test item (37, 74, 92.5 and 111 MBq of [188Re]rhenium-ImDendrim, respectively) compared to control lots (free [188Re]rhenium and non-radioactive ImDendrim). By the end of the study in six weeks post-test compound administration, the tumors were collected for histological analysis. Results: The treatment was well tolerated. In fact, [188Re]rhenium-ImDendrim shows high significant anti-tumor property in this experimental cancer model even with the lowest dose of 37 MBq compared to control groups. These results were further confirmed by histological analysis. Large tumor mass only observed in tumor's sections from mice in the control groups, were disappeared in favour of collagen tissue in treated groups. In conclusion, this novel potential radiopharmaceutical agent has giving promising experimental results by showing an anti-tumoral activity in this experimental of liver cancer model in mice under the tested conditions.

Keywords

Hepatocellular , Carcinoma, Dendrimer , Anticancer agent, Nanomedicine

ImDendrim - Cet article est dedié à la mémoire de Hamza BELHADJ-TAHAR (1921-1995)


Symposium du CHU Tangji - Les travaux de recherche (rapportés dans cet article) ont été encouragés au cours de ce meeting


Radiopharmacien de l'équipe du CHU Tangji,Shanghai - Cet anticacéreux a été developpé au sein de cette équipe en collaboration avec AFPREMED


Radiopharmaceutiques

- Voici quelques publications en lien avec les radiopharmaceutiques du Dr Belhadj-Tahar

1. Synthesis, Characterization and Biodistribution Of New 99mTc Oxo and Nitrido Complexes with Bi and Tetradendate Unsaturated NS and N2S2 Schiff Bases Derived from 2-Aminocyclopentene-1-Dithio Carboxylic Acid as Possible Heart Imaging Agents.
Y. COULAIS, G. CROS, M. H. DARBIEU, J.A.M. TAFANI, H. BELHADJ-TAHAR, E. BELLANDE, R. PASQUALINI and R. GUIRAUD.
Nucl. Med. Biol., 1994, 21, 263-268.

2. Synthesis and characterization of neutral oxorhenium(V) and nitridotechnetium(V) complexes with a tetradendate N2S2 unsaturated ligand derived from dithiocarboxylic acid.
G. CROS, H. BELHADJ-TAHAR, D. De MONTAUZON, A. GLEIZES, Y. COULAIS, R. GUIRAUD, E. BELLANDE and R. PASQUALINI.
Inorg. Chim. Acta, 1994, 227, 25-31.

3. Synthesis and Characterization of oxo and nitrido complexes of Technetium-99(V) and Rhenium(V) with new SNO and SN2O ligands:Biodistribution study of the related 99mTc-complexes.
G. CROS, Y. COULAIS, H. BELHADJ-TAHAR, A. GLEIZES and R. GUIRAUD
In: Technetium and Rhenium in Chemistry and Nuclear Medicine,
Edited by Nicolini M., Bandoli G. and Mazzi U., Servizi Grafici Editoriali, Padova, 1994, pp. 85-87.

4. Technetium Labelling of Bi, Tri and Tetradentate Ligands Derived from 2-Aminocyclopentene-1-Dithiocarboxylic Acid. Characterization and Biodistribution of their Oxo and Nitrido 99m-Technetium Complexes. H. BELHADJ-TAHAR, Y. COULAIS, G. CROS, M.H. DARBIEU, J.A.M. TAFANI,J. FABRE, J. P. ESQUERRE and R. GUIRAUD Nucl. Med. Biol., 1996, 23, 353-357. [521 KB] 5. Synthesis and Biodistribution of New Oxo and Nitrido 99mTc Complexes with Asymetrical Potentially Dianionic or Trianionic Tetradentate SNNO Ligands Derived from Methyl-2-aminocyclopentene-1-dithiocarboxylic Acid. H. BELHADJ-TAHAR, E. OUHAYOUN, G. CROS, M.-H. DARBIEU, J. A. M. TAFANI, J. FABRE, J. P. ESQUERRE and Y. COULAIS Nucl. Med. Biol., 1998, 25, 65-70. [519 KB]

6. Chimie du Rhénium H. BELHADJ-TAHAR, G. CROS, M. DARTIGUENAVE
In:"Radiopharmaceutiques. Chimie des Radiotraceurs et Applications Biologiques, Grenoble Sciences, COMET, M.; Vidal, M. (Ed.) Presses Universitaires de Grenoble, Grenoble (France), 1998, pp. 181-204.

7. Cement of Hydroxyapatit Loaded with 99Technetium and 185/187Rhenium.
H. BELHADJ-TAHAR, A. BOUNEDER, J.-L. BUTOUR, Y. COULAIS, M.-H. DARBIEU, C. MARBEZY, J.-P. TUCHAGUES and J.-L. LACOUT
In "Technetium and Rhenium in Chemistry and Nuclear Medicine"
Edited by M. Nicolini, G. Bandoli and U. Mazzi (Ed.) Servizi Grafici Editoriali, Padova, Italy, 1999,.883-840.

8. Synthesis and Physico-Chemical and Biological Characterization of New Nitrido 99mTechnetium Complexes with Asymmetric Tetradentate SN3-Type Ligands Derived from the Methyl-2-[(b-aminoethyl)amino]cyclopent-1-enedithiocarboxylate Ester.
H. BELHADJ-TAHAR, Y. COULAIS, M.-H. DARBIEU and J.-P. TUCHAGUES
In "Technetium and Rhenium in Chemistry and Nuclear Medicine"
Edited by M. Nicolini, G. Bandoli and U. Mazzi (Ed.) Servizi Grafici Editoriali, Padova, Italy, 1999, 669-676.

9. Conceptionalization of diagnostic agents : From empirical in vivo screening to rational in vitro predictive parameters.
BELHADJ-TAHAR, R. BOUMAHDI and M.-H. DARBIEU
Alternative To Laboratory Animals (ATLA), 2000, 28, 303-314

10. Biological behavior studies of labelled dithiocarboxylic acid derivatives.
BELHADJ-TAHAR, Y. COULAIS et M. FABRE
Veterinary and Human Toxicolgy, 2001, vol. 43, 4, 244.

11. Tetragastrine derivative (S-EOE-MAG3-b-alanine-CCK4): Synthesis, 99m/99Technetium and 185/187Rhenium labelling and biological studies
BELHADJ-TAHAR, M.H. DARBIEU, J.P. ESQUERRE ET Y. COULAIS
In "Technetium and Rhenium in Chemistry and Nuclear Medicine"
Edited by M. Nicolini and U. Mazzi (Ed.) Servizi Grafici Editoriali, Padova,
Italy, 2002, 323-327.

12. Application de la chimie de coordination du technetium-99 dans le domaine de la biologie et de la médecine.
BELHADJ-TAHAR ET M-H. DARBIEU
L’Actualité Chimique, 2003, 11-12 : 57-63

13. Développement des Radiopharmaceutiques : Implication des complexes métalliques oxo et nitruro technétium-99 et rhénium à l’échelle pondérale.BELHADJ-TAHAR, M-H. DARBIEU et G. CAMPISTRONMédecine Nucléaire- Imagerie Fonctionnelle et Métabolique, 2004, 28(3) : 101-109 [850 KB]

14. In vivo renal parenchyma exploration by [99mTc]-di-Mercaptosuccenic complex in search of procalcitonin implication in apoptosis paradigm .
BELHADJ-TAHAR , Y. Coulais, R. RUMEAU and F. BOUISSOU
In "Technetium and Rhenium in Chemistry and Nuclear Medicine"
Edited by M. Nicolini and U. Mazzi (Ed.) Servizi Grafici Editoriali, Padova,
Italy, 2006, 7:635-8

15. An easy-to-use imaging tool and radiopharmaceutical agent derived from CCK4 for internal therapy: Synthesis an assessment for an original biovectorBELHADJ-TAHAR,JP ESQUERRE and Y. COULAIS Nuclear Instruments and Methods in Physics Research, 2006, 571:146-150 [158 KB] 16. Expertise nanotoxicologique : expérience toulousaine.
BELHADJ-TAHAR, F. GROSS, A.Z. BOUSSEKSOU and L. BUSCAIL.
Bull. Cancer, 2011 vol. 98 (2) :50-51

17. Radiolabeling of [18F]-fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for imaging the PCP sites of NMDA receptors.
A-S SALABERT, C FONTA, C FONTAN, A DJILALI, M TAFANI, C PESTOURIE, H BELHADJ-TAHAR, M ALONSO, P PAYOUX
Nuclear Medicine and Biology, 2015, Volume 42 (8), 643–653

II- Patents

18. Novel chemical compounds derived from normemantine and use of same in the medical field.
O GUERRET; S DUFOUR; H BELHADJ-TAHAR
PCT NO: PCT/EP2014/060981

19. Dendrimer compositions, methods of synthesis, and uses thereof.
H BELHADJ-TAHAR, N SADEG, Y COULAIS
PCT NO: PCT/IB2014/058238

Poster

Etudes de Toxicocinétique et de biodistribution de dendrimèresde cinquième générationHafid BELHADJ-TAHAR, Clément FAYE, Thomas REGNIER, Laurent GARRELLY, BertrandNASSAR et Yvon COULAIS [124 KB]


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