Noninvasive monitoring of colonic carcinogenesis: feasibility of [(18)F]FDG-PET in the azoxymethane model

M. van Kouwen, P. Laverman, J. van Krieken, W. Oyen, F. Nagengast and J. Drenth

Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, 6500 HB Nijmegen, The Netherlands.
Feb, 2006



Azoxymethane (AOM) is a potent carcinogen that induces colorectal cancer and adenomas in rats. [(18)F]FDG-PET is a molecular imaging technique that is based on the elevated uptake and retention of radiolabeled glucose. At present, it is unknown at which stage FDG accumulation occurs during the adenoma carcinoma sequence. To address this issue, we studied the FDG uptake in AOM-induced rat colorectal adenocarcinoma (CRC) and correlated this with histopathological findings.Seventy Fischer 344 rats were injected with AOM. Terminal autopsy took place 20-38 weeks after the first AOM injection. After [(18)F]FDG PET scanning, the rats were sacrificed, tissue [(18)F]FDG uptake was measured, followed by histopathological examination.Macroscopic examination revealed 21 tumors (7 located in the small bowel and 14 in the colon) in 19 rats. On histological examination, we found 10 colonic adenocarcinomas (the first being observed at Week 22) and 7 adenocarcinoma in the small bowel. In total, seven colon adenomas were found in five rats, six of which expressed high-grade dysplasia. The [(18)F]FDG accumulation in small intestine carcinomas was well beyond background accumulation (P<.0001). On PET scanning, two rats showed focal accumulation of the abdominal area, corresponding to small intestine carcinomas.Adenocarcinomas had a significantly higher [(18)F]FDG uptake than background bowel uptake. [(18)F]FDG uptake was lower in adenomas than in carcinomas. These data suggest that the AOM model allows the evaluation of intervention strategies with [(18)F]FDG uptake as a valid outcome measure.