Tumour microenvironment heterogeneity affects the perceived spatial concordance between the intratumoural patterns of cell proliferation and ¹⁸F-fluorothymidine uptake

Background and purpose: PET imaging with ¹⁸F-fluorothymidine (¹⁸F-FLT) can potentially be used to identify tumour subvolumes for selective dose escalation in radiation therapy. The purpose of this study is to analyse the co-localization of intratumoural patterns of cell proliferation with ¹⁸F-FLT tracer uptake. Materials and methods: Mice bearing FaDu or SQ20B xenograft tumours were injected with ¹⁸F-FLT, and bromodeoxyuridine (proliferation marker). Ex vivo images of the spatial pattern of intratumoural ¹⁸F-FLT uptake and that of bromodeoxyuridine DNA incorporation were obtained from thin tumour tissue sections. These images were segmented by thresholding and Relative Operating Characteristic (ROC) curves and Dice similarity indices were evaluated. Results: The thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation were significantly different for the two xenograft tumour models, whereas the median Dice values were not. However, ROC analysis indicated that segmented FLT images were more specific at detecting the proliferation pattern in FaDu tumours than in SQ20B tumours. Conclusion: Highly dispersed patterns of cell proliferation observed in certain tumours can affect the perceived spatial concordance between the spatial pattern of ¹⁸F-FLT uptake and that of cell proliferation even when high-resolution ex vivo autoradiography imaging is used for ¹⁸F-FLT imaging.