[Contribution of microCT structural imaging to preclinical evaluation of hepatocellular carcinoma chemotherapeutics on orthotopic graft in ACI rats].

Fiche publication


Date publication

février 2011

Auteurs

Membres identifiés du Cancéropôle Est :
Pr MARESCAUX Jacques


Tous les auteurs :
Akladios CY, Bour G, Balboni G, Mutter D, Marescaux J, Aprahamian M

Résumé

Animal experimentation is a prerequisite for preclinical evaluation of treatments such as chemotherapy. It's strictly regulated with the purpose of reducing the number of experimental animal as well as their pain. Small animal imaging should provide a painless longitudinal follow up of tumor progression on a single animal. The aim of the study is to validate small animal imaging by microscanner (muscan) in longitudinal follow up of a hepatocellular carcinoma (HCC) and to demonstrate its interest for in vivo evaluation of tumor response to different therapeutics. An HCC model achieved by orthotopic graft of the MH3924A cell line in ACI rats was followed using a Imtek/Siemens microscanner (muscan) with contrast agents (Fenestra((R)) LC/VC). The procedures giving the optimal enhancement of the liver as well as a reliable determination of tumor volumes by muscan were validated. Three protocols for therapeutic assessment through muscan longitudinal follow up were performed. Each consisted in three groups testing a chemotherapy (gemcitabine, gemcitabine-oxaliplatine or sorafenib) versus two control groups (placebo and doxorubicine). Comparison was done on tumor volumes, median and actual survivals. There was a significant correlation between tumor volumes measured by muscan and autopsy. Treatment by sorafenib, at the contrary of gemcitabine alone or with oxaliplatine, resulted in a significant reduction in tumor volumes and prolongation of actuarial survival. These results are consistent with available clinical data for these diverse therapeutics. In conclusion, small animal imaging with muscan is a non-invasive, reliable, and reproducible method for preclinical evaluation of antitumor agents.

Référence

Bull Cancer. 2011 Feb 1;98(2):120-32.