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Background and Purpose: FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrates accelerated tumor repopulation during fractionated irradiation with pathological validation (Ki-67 and BrdUrd makers) in a xenograft model system. However, these and other functional assays must be performed ex vivo and post hoc. We propose a novel, in vivo, real-time assay utilizing (18)F-FLT PET., Material and Methods: Nude mice with FaDu-hSCC were irradiated with 12 or 18 fractions of 1.8 Gy ([Dm]=3.0 Gy), either daily or every second day. (18)F-FLT micro-PET scans were performed at different time points, FLT parameters (SUVmax, SUVmean, and T/NT) were measured. Tumor sections were stained for Ki-67 and BrdUrd, a labeling index (LI) was calculated. Imaging-pathology correlation was determined by comparing FLT parameters and immunohistochemical results., Results: Measured SUVmax, SUVmean and T/NT decreased significantly after daily irradiation with 12 fractions in 12 days (P<0.05) and 18 fractions in 18 days (P<0.05). In contrast, these parameters increased in mice treated with 12 fractions in 24 days (P>0.05) and 18 fractions in 36 days (P>0.05), suggesting accelerated repopulation. Similarly, Ki-67 and BrdUrd LIs demonstrated significant decreases with daily irradiation (P<0.05), and increases with every-second-day irradiation (P>0.05). (18)F-FLT parameters correlated strongly with proliferation markers (r(2): 0.679-0.879, P<0.001)., Conclusions: (18)F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for (18)F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: The primary aim of this study was to use serial (18)F-3'-deoxy-3'-fluorothymidine (FLT) PET/CT to measure tumor cell proliferation during radiotherapy of squamous cell carcinoma (SCC) of the esophagus., Methods: Twenty-one patients with inoperable locally advanced SCC of the esophagus underwent serial (18)F-FLT PET/CT during radiotherapy. Each patient received a pretreatment scan, followed by 1-3 scans after delivery of 2, 6, 10, 20, 30, 40, 50, or 60 Gy to the tumor., Results: Among the 19 patients who completed radiotherapy without interruption, parameters reflecting (18)F-FLT uptake in the tumor (i.e., maximum tumor standardized uptake value [SUVmax] and proliferation target volume) decreased steadily. All patients demonstrated an almost complete absence of proliferating esophageal tumor after 30 Gy and a complete absence after 40 Gy. In the 2 patients whose radiotherapy course was interrupted, (18)F-FLT uptake in the tumor was greater after the interruption than before the interruption. Marked early reduction of (18)F-FLT uptake in irradiated bone marrow was observed in all patients, even after only 2 Gy. All showed a complete absence of proliferating marrow in irradiated regions after 10 Gy. Both patients who underwent scans after completing the entire radiotherapy course showed no tumor uptake on (18)F-FLT PET/CT but high uptake on (18)F-FDG PET/CT. Pathologic examination of these regions revealed inflammatory infiltrates but no residual tumor., Conclusion: (18)F-FLT uptake can be used to monitor the biologic response of esophageal SCC and normal tissue to radiotherapy. Increased uptake of (18)F-FLT after treatment interruptions may reflect accelerated repopulation. (18)F-FLT PET/CT may have an advantage over (18)F-FDG PET/CT in differentiating inflammation from tumor.