Fibroblast Activation Protein and Glycolysis in Lymphoma Diagnosis: Comparison of 68Ga-FAPI PET/CT and 18F-FDG PET/CT.

ABSTRACT

Our objective was to compare the diagnostic performance of 68Ga-labeled fibroblast activation protein (FAP) inhibitor (FAPI) and 18F-labeled FDG PET/CT in diagnosing lymphomas and to characterize the influence of FAP and glycolytic markers on tracer uptake by involved lesions. Methods: Participants with different lymphoma subtypes who were prospectively recruited from May 2020 to December 2021 underwent 68Ga-FAPI and 18F-FDG PET/CT. Immunohistochemistry was performed to evaluate FAP, hexokinase 2, and glucose transporter 1 (GLUT1) expression, and the paired-samples t test and Wilcoxon signed-rank test were used to compare parameters. The correlation between the immunochemistry results and tracer uptake was determined by the Spearman rank correlation coefficient. Results: In total, 186 participants (median age, 52 y [interquartile range, 41-64 y]; 95 women) were included. Dual-tracer imaging produced 3 types of imaging profiles. 18F-FDG PET possessed a higher staging accuracy (98.4%) than 68Ga-FAPI PET (86.0%). In 5,980 lymphoma lesions, 18F-FDG PET/CT detected more nodal (4,624 vs. 2,196) and extranodal (1,304 vs. 845) lesions than 68Ga-FAPI PET/CT. Additionally, 52 68Ga-FAPI-positive/18F-FDG-negative lesions and 2,939 68Ga-FAPI-negative/18F-FDG-positive lesions were observed. In many lymphoma subtypes, semiquantitative evaluation revealed no significant differences in SUVmax or target-to-liver ratios between 68Ga-FAPI and 18F-FDG PET/CT (P > 0.05). Interestingly, GLUT1 and hexokinase 2 were overexpressed both in lymphoma cells and in the tumor microenvironment, whereas FAP was expressed only in stromal cells. FAP and GLUT1 expression correlated positively with 68Ga-FAPI SUVmax (r = 0.622, P = 0.001) and 18F-FDG SUVmax (r = 0.835, P < 0.001), respectively. Conclusion: 68Ga-FAPI PET/CT was inferior to 18F-FDG PET/CT in diagnosing lymphomas with low FAP expression. However, the former may supplement the latter and help reveal the molecular profile of lymphomas.