ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common cancer related deaths worldwide. One of the main challenges in cancer treatment is drug delivery to target cancer cells specifically. Preclinical evaluation of intratumoral drugs in orthotopic liver cancer mouse models is difficult, as percutaneous injection hardly can be precisely performed manually. In the present study we have characterized a hepatoma model developing a single tumor nodule by implantation of Hep55.1C cells in the liver of syngeneic C57BL/6J mice. Tumor evolution was followed up by µCT imaging, and at the histological and molecular levels. This orthotopic, poorly differentiated mouse HCC model expressing fibrosis, inflammation and cancer markers was used to assess the efficacy of drugs. We took advantage of the high precision of a previously developed robotized system for automated, image-guided intratumoral needle insertion, to administer every week in the tumor of the Hep55.1C mouse model. A significant tumor growth inhibition was observed using our robotized system, whereas manual intraperitoneal administration had no effect, by comparison to untreated control mice.
Subject(s)
Carcinoma, Hepatocellular/pathology , Drug Evaluation/instrumentation , Liver Neoplasms/pathology , Robotics , X-Ray Microtomography , Animals , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Mice , Mice, Inbred C57BL , Xenograft Model Antitumor AssaysABSTRACT
The development of imaging devices adapted to small animals has opened the way to image-guided procedures in biomedical research. In this paper, we focus on automated procedures to study the effects of the recurrent administration of substances to the same animal over time. A dedicated system and the associated workflow have been designed to percutaneously position a needle into the abdominal organs of mice. Every step of the procedure has been automated: the camera calibration, the needle access planning, the robotized needle positioning, and the respiratory-gated needle insertion. Specific devices have been developed for the registration, the animal binding under anesthesia, and the skin puncture. Among the presented results, the system accuracy is particularly emphasized, both in vitro using gelose phantoms and in vivo by injecting substances into various abdominal organs. The study shows that robotic assistance could be routinely used in biomedical research laboratories to improve existing procedures, allowing automated accurate treatments and limited animal sacrifices.
