Spatial Concordance of Tumor Proliferation and Accelerated Repopulation from Pathologic Images to 3′-[ 18 F]Fluoro-3′-Deoxythymidine PET Images: a Basic Study Guided for PET-Based Radiotherapy Dose Painting

Purpose To assess tumor cell proliferation and repopulation during fractionated radiotherapy and investigate the spatial concordance of cell proliferation and repopulation according to the uptake of 3′-[ 18 F]fluoro-3′-deoxythymidine ([ 18 F]FLT). Procedures Mice bearing A549 xenograft tumors were assigned to five irradiated groups, including 3 fraction (f)/6 days (d), 6f/12d, 9f/18d, 12f/24d, and 18f/36d with 2 Gy/f irradiations performed every other day and one non-irradiated group. Serial [ 18 F]FLT positron emission tomography (PET) scans were performed at different time points as the groups finished the radiotherapy. The maximum of standard uptake values (SUVmax) were measured to confirm the likely time of tumor repopulation. A layer-by-layer comparison between SUVmax of PET images and Ki-67 LI of pathology images, including the thresholds at which maximum overlap occurred between FLT-segmented areas and cell proliferation areas were conducted to evaluate the spatial correlation. Results The SUVmax decreased in the 3f/6d group ( P = 0.000) compared to the non-irradiated group, increased in the 6f/12d group and then gradually reduced with prolonged treatment. Proliferation changes in 6f/12d group on pathology images were also confirmed. Significant correlations were found between the SUVmax and Ki-67 LI in each in vitro tumor of cell proliferation group and accelerated repopulation group (both of the P < 0.001). Furthermore, the mean overlap region rates (ORRs) were 56.21 % and 57.82 % in the proliferation group and repopulation group, respectively. The data represented the preferable registration. Conclusions [ 18 F]FLT PET is a promising imaging surrogate of tumor proliferative response to fractionated radiotherapy and may help make an adaptive radiation oncology treatment plan to realize radiotherapy dose painting.