Histopathologic validation of 3′-Deoxy-3′-¹⁸F- fluorothymidine PET for detecting tumor repopulation during fractionated radiotherapy of human FaDu squamous cell carcinoma in nude mice

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 ¹⁸F-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. ¹⁸F-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). ¹⁸F-FLT parameters correlated strongly with proliferation markers (r²: 0.679-0.879, P < 0.001). Conclusions ¹⁸F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for ¹⁸F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy.