A striking feature of neoplastic cells is their exceptionally high rate of glycolysis compared to normal tissue.
Our aim i s to exploit this biological difference as a sensitive diagnostic tool and a specific indicator of response to tumor-directed treatment. Glucose uptake and phosphorylation will be estimated using [18F]-2-fluoro-2-deoxyglucose (18FDG) and positron emission tomography (PET). Any detected alteration in tumor metabolism will be compared to conventional measurements of tumor response. Specifically, our proposed studies are designed to demonstrate that PET can measure early changes in glucose metabolism following chemotherapy and particularly, thermochemo-therapy, because such treatment should cause rapid alterations in tumor metabolism. It is our assumption that early detection of tumor response to therapy will favorably affect the ultimate therapeutic outcome by allowing prompt modification of treatment. Preliminary studies are presented which have indicated that (1) metabolic imaging with PET detects glucose metabolism in metastatic tumor; (2) it is likely to be a more sensitive method that conventional techniques; (3) it can show metabolic changes in response to therapy, and (4) it shows metabolic changes in tumor 10 days after heat alone. We now propose to confirm these initial observations. Sixty patients with liver metastases from colon cancer will be treated with either a chemotherapy regimen (40 patients) or with whole body (WBH) hyperthermia combined with the same chemotherapy regimen (thermo-chemotherapy) (20 patients). The glucose metabolism of the metastases will be measured by PET imaging with 18FDG. Uptake and metabolic rate of 18FDG will be estimated prior to treatment in all patients, as well as 28 days after treatment. While pre-clinical data suggest that thermo-chemotherapy will cause a more rapid and a greater tumor response than will chemotherapy alone, these studies are specifically designed to determine if, at one month, a response to either a regimen of chemotherapy or to thermo-chemotherapy can be determined, and to give an indication of the relative sensitivity of individual liver metastases to chemotherapy versus the combined therapy. It is expected that metabolic imaging of tumor metastases with 18FDG and PET will be more specific and more sensitive indicator of tumor status than any other technique hitherto available. This information will broadly impact the entire field of clinical cancer therapy.
