Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer

Pancreatic cancer is one of the most incurable and lethal human cancers in the United States. To facilitate development of novel therapeutic agents, w e previously established an orthotopic pancreatic tumor model that closely mimics the natural biological behavior of human pancreatic cancer. In this study, magnetic resonance imaging (MRI) techniques were developed to detect tumor formation noninvasively and monitor serially tumor growth kinetics i n this orthotopic model used for experimental drug testing. By using an opt imized T2-weighted imaging method, we were able to distinguish human pancre as cancer from normal mouse pancreas. Orthotopic tumor formation was detect ed as early as day 11 after tumor cell implantation with a tumor volume as small as 12 mm(3). Mice with evidence of tumor were separated into four tre atment groups: control, auristatin-PE, gemcitabine, and their combination. After treatment, the mice were imaged at least three times before terminati on of the experiment. Comparison between MRI tumor volume measurements and tumor weights made at biopsy resulted in a correlation coefficient of 0.98. The tumor growth curves constructed from serial magnetic resonance imaging (MRI) measurements clearly showed tumor growth inhibition in treated mice compared with the control group. As expected, the group treated with the co mbination had the highest response rate compared with either auristatin-PE or gemcitabine alone, and the data were statistically highly significant (p < 0.004). From these results, we conclude that noninvasive MRI can be used to monitor serially therapeutic response in this orthotopic human pancreat ic tumor model and can be used in the future to evaluate novel antitumor ag ents before human studies.