Biological image-guided radiotherapy in rectal cancer: Is there a role for FMISO or FLT, next to FDG?

PURPOSE: The purpose of this study is to investigate the use of PET/CT with fluorodeoxyglucose (FDG), fluorothymidine (FLT) and fluoromisonidazole (FMISO) for radiotherapy (RT) target definition and evolution in rectal cancer. MATERIALS AND METHODS: PET/CT was performed before and during preoperative chemoradiotherapy (CRT) in 15 patients with resectable rectal cancer. PET signals were delineated and CT images on the different time points were non-rigidly registered. Mismatch analyses were carried out to quantify the overlap between FDG and FLT or FMISO tumour volumes (TV) and between PET TVs over time. RESULTS: Ninety sequential PET/CT images were analyzed. The mean FDG, FLT and FMISO-PET TVs showed a tendency to shrink during preoperative CRT. On each time point, the mean FDG-PET TV was significantly larger than the FMISO-PET TV but not significantly larger than the mean FLT-PET TV. There was a mean 65% mismatch between the FMISO and FDG TVs obtained before and during CRT. FLT TVs corresponded better with the FDG TVs (25% mismatch before and 56% during CRT). During CRT, on average 61% of the mean FDG TV (7 cc) overlapped with the baseline mean TV (15.5 cc) (n=15). For FLT, the TV overlap was 49% (n=5) and for FMISO only 20% of the TV during CRT remained inside the contour at baseline (n=10). CONCLUSION: FDG, FLT and FMISO-PET reflect different functional characteristics that change during CRT in rectal cancer. FLT and FDG show good spatial correspondence, while FMISO seems less reliable due to the non-specific FMISO uptake in normoxic tissue and tracer diffusion through the bowel wall. FDG and FLT-PET/CT imaging seem most appropriate to integrate in preoperative RT for rectal cancer.