Measuring Tumor Cell Proliferation with 18F-FLT PET During Radiotherapy of Esophageal Squamous Cell Carcinoma: A Pilot Clinical Study

Abstract

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. 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. 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. (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.