This investigation was undertaken to evaluate F-18-labeled fluorodeoxyglucose (FDG) PET in monitoring patients after intraoperative radiotherapy (IORT) for unresectable pancreatic cancer and to compare its usefulness with CT. Methods: FDG PET was performed in 12 consecutive unresectable ductal adenocarcinoma patients before (n = 12) and after IORT (0.7-11.9 mo, n = 14). In the follow-up period, FDG PET results after IORT were divided into three groups: early (0-2.0 mo after IORT, n = 7), intermediate (2.1-4.0 mo, n = 5) and delayed period (4.1 mo or later, n = 2). FDG uptake at 60 min after injection of 185 MBq FDG under fasting conditions was analyzed with standardized uptake value (SUV). Three parameters, the highest SUV in the tumor, the area of tumor showing SUV of more than 2.0 and the average SUV in the tumor area were calculated. Ratios of each parameter after IORT to that before IORT were defined as residual uptake ratio (RUR)-1, -2 and -3, respectively. Tumor regression after IORT was evaluated with CT as tumor size ratio (TSR) every 2 mo. Results: Results of RUR-1 and -3 were consistent with tumor size measured by CT. They decreased in 10 patients with partial response and increased in 2 patients with no change, although these 2 patients had abscesses. RUR-3 decreased consistently as 0.65 +/- 0.33 in 2 mo, 0.51 +/- 0.39 in 4 mo and 0.24 in 4 mo or later after IORT, respectively. RUR-1 decreased in early period, but demonstrated no change through the remaining periods. There were discrepancies between the results of RUR-2 and those of the other RURs. CT results revealed a slow decrease in tumor size, because TSR was 0.91 +/- 0.10, 0.76 +/- 0.11 and 0.70 +/- 0.18 in 2, 4 and 6 mo after IORT, respectively. RUR-3 was smaller than TSR at 2 mo (P < 0.05) and 4 mo (P = 0.056). These results indicate that the measurement of the average SUV in the tumor area with FDG PET could evaluate the local response of pancreatic cancer after IORT earlier and more markedly than with CT. Conclusion: FDG PET was useful in monitoring patients after IORT, because the decrease of metabolism in pancreatic tumor could be detected earlier than the decrease in tumor size.