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

Abstract

Background and purposePET 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 methodsMice 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. ResultsThe 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. ConclusionHighly 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.