Spatiotemporal voxel-wise concordance between ⁶⁸Ga-FAPI and ¹⁸F-FDG PET/CT: association with pathologic response in esophageal squamous cell carcinoma receiving neoadjuvant chemoradiotherapy.

Abstract

This study aimed to investigate the spatiotemporal correlation between tumor metabolism and cancer-associated fibroblast activity using dual-tracer PET/CT, and to explore their potential association with pathologic response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC). This retrospective analysis of a prospective trial (ChiCTR2100051599) included 48 patients with ESCC from February 2022 to August 2024. All patients underwent ⁶⁸Ga-FAPI and ¹⁸F-FDG PET/CT before pre-nCRT (S1) and after nCRT (S2). Two primary metrics were used to quantify their spatial correlations by voxel-wise correlation analyses: the SUV Correlation Coefficient (SUV_R), reflecting static uptake concordance, and the Dose-Response Matrix Correlation Coefficient (DRM_R), reflecting concordance in treatment dose sensitivity. The conventional parameters derived from FAPI- and FDG- PET were also extracted: SUV_max, SUV_mean, SUV_CV, SUV_maxratio, SUV_meanratio, DRM_max, DRM_median, DRM_CV and the resistant tumor volume (V(DRM_> 0.7)). The associations of these metrics with pathological tumor regression grade (TRG) were evaluated in an exploratory manner, except for DRM-related metrics. A strong voxel-wise correlation was observed between pre-nCRT FAPI and FDG uptake (S1 SUV_R = 0.80 ± 0.17), which was weaker after nCRT (S2 SUV_R = 0.51 ± 0.23). Two dose-response matrices showed a strong correlation (DRM_R = 0.82 ± 0.14). The bivariate Logistic model, integrating the post-treatment SUV_R and SUV_CV_FDG, significantly predicted pathological response (p = 0.007), achieving an optimization-corrected AUC of 0.78 (95%CI: 0.62-0.95). The pre-nCRT tumor voxel intensity and dose response constructed using either FDG or FAPI PET imaging exhibited a strong spatial correlation. In this exploratory analysis, the post-nCRT FAPI-FDG correlation coefficient was associated with pathologic response when combined with SUV_CV_FDG in a Logistic model.