Computed tomographic colonography is a reliable procedure to assess efficacy of chemopreventive agents in living animals: Evaluation of aspirin-DFMO combination.

Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 B76 Computed tomographic (CT) colonography offers the advantage to be a non-invasive cross-sectional imaging examination that can reliably detect colorectal lesions. Chemopreventive studies with preclinical models have been hindered by the impossibility to follow in the same living animal the formation of polyps and their transition to carcinoma. In this regard, the use of CT colonography for the follow-up of tumorigenesis may offer a new tool for chemoprevention research. Our objectives were to assess by CT colonography the chemopreventive efficacy of apirin and difluoromethylornithine (DFMO) given in combination. Aspirin is known to lower prostaglandin concentration in tissues and DFMO is a well known irreversible inhibitor of ornithine decarboxylase a key enzyme in polyamine synthesis. These agents were found to be more efficient when associated than when administered separately and clinical data support the use of DFMO and aspirin in combination as a strategy for colon cancer prevention in humans. Fischer rats received an intraperitoneal injection (25 mg/kg) of the chemical carcinogen dimethylhydrazine (DMH) once a week for two weeks in order to initiate colon carcinogenesis. Rats were then randomly separated into control (3 animals, group C) and experimental groups (6 animals, group E). Five months following the last DMH injection, at a stage where tumors may already be present, a first CT colonography was performed on all rats. Thereafter rats of the experimental group received a 0.1% mixture of aspirin and DFMO in their drinking water. The daily intake of aspirin and DFMO per rat was 60 mg/kg body weight (360 mg/m2) for each compound. CT colonography was then performed at 6, 7 and 8 months. Rats received oraly a gut cleaning solution during 3 days before CT colonography. After a 24 h starvation period just before CT colonography a contrasting solution (20 mL) was administered intrarectaly to the anesthetized rat. CT colonography was performed with a micro-CT scanner Micro Cat II (Imtek Inc., San Diego, USA). Rats were scanned in supine position under anesthesia. The MicrocatTM software allowed a 3D reconstruction process from the 2D-X ray images. Axial, sagital and coronal views were obtained. Data showed a precise correlation between localization and size of tumors found at autopsy and those detected by CT colonography. In rats with tumors at the start of the aspirin/DFMO treatment, a 3 fold diminution of tumorigenesis was observed. In rats where no tumors were detected at the beginning of the aspirin/DFMO treatment, tumor formation was completely inhibited. This is the first report showing that CT colonography represents a very attractive method for the follow-up of chemopreventive trials in living animals.