LB-290

Piroxicam feeding (d0-14) induces colitis and cancer in IL-10-/- mice. Here we report on findings of 14.1T mouse MR imaging of the progression of colitis in IL-10-/- mice to dysplasia and cancer and effects of TNF blockade. MRI imaging detected increased wall thickness in areas of severe colitis, high grade dysplasia and cancer compared to controls. Anti-TNF mAb (.5mg murine chimeric mAb x 1) reduced colon wall thickness by 45-55% within 7 days. Normal, colitic and cancerous colons were further characterized by differences in T1 and T2 relaxation times on live animals and excised colons. All three colonic layers (mucosa, submucosa, muscularis) were affected by inflammation in colitis, high grade dysplasia and cancer. Acute colitis caused marked increases in thicknesses of all three colon layers. In controls, T1 and T2 relaxation times exhibited uniform T1 (1.36±0.10s) and T2 (16.01±1.72msec) values throughout the colon wall. In colitic mice, T1 and T2 values were prolonged in submucosal (T1: 1.81±0.07s, T2:15.65±1.15msec) and mucosal and muscularis layers (T1:2.41±0.18s, T2:19.21±0.80msec. In areas of histology-confirmed dysplasia and cancer, mucosal T2 values increased by 37% and 46% respectively (26.11±1.19 and 28.63±0.92msec) compared to mucosal T2 values in colitis (above). These studies demonstrate that in vivo MR imaging accurately assesses the progression of mucosal inflammatory effects on colonic mucosa. Furthermore, data suggest that as mucosal inflammation accelerates and makes the transition to dysplasia, T2 relaxation times prolong. The attractive implication is that MR imaging may provide noninvasive means for alerting physicians to early dysplasia in colitis. Furthermore, these results raise the possibility that anti-TNF therapy may impede the progression from colitis to dysplasia Acknowledgement: Supported by Centocor, PHS NIAID 1R01AI061701

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA