This project is designed to use NMR to follow the progressive development of hepatocellular carcinoma in the rat following treatment with chemical carcinogens. Using a modified Toronto (Solt-Farber) protocol, one may treat animals over an initial two-week period and follow the appearance of progressively more agressive cell populations (nodules), hepatocellular carcinoma, and eventually metastatic carcinoma at 10 to 16 months. Six to eight weeks after the initiation of treatment, there are 50-150 nodules ranging in size from 0.1 to 3 mm. Most of these regress so that by 4-5 months, only a few (3-8) nodules persist. Eventually these give rise to carcinoma. We will use a Biospec 310/2.3 imaging system to study this process. We will first image isolated nodules to develop appropriate imaging parameters (time, slice thickness, repetition times, etc.). We will then apply this information to imaging in vivo. Specifically, we will test the hypothesis that most hepatocellular carcinomas rise in persistent nodules by periodic imaging of these nodules in vivo. We will correlate imaging parameters (e.g., relaxation times) with biological phenomena including in situ hybridization for oncogene expression and the biological behavior of excised transplanted nodules or cell lines made from them. We will also image metastases found in these animals. To extend the generality of our findings we will employ the carcinogen/phenobarbital protocol for tumor induction on a comparative basis with the modified Toronto protocol.
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