Fibroblast Activation Protein and Glycolysis in Lymphoma Diagnosis: Comparison of<sup>68</sup>Ga-FAPI PET/CT and<sup>18</sup>F-FDG PET/CT
Xuetao Chen, Shuai Wang, Yumei Lai, Guochang Wang, Maomao Wei, Xiao Jin, Jin Ding, Yan Zhang, Yunfei Shi, Feng Wang, Hua Zhu, Zhi Yang, Xuejuan Wang
Abstract
Our objective was to compare the diagnostic performance of <sup>68</sup>Ga-labeled fibroblast activation protein (FAP) inhibitor (FAPI) and <sup>18</sup>F-labeled FDG PET/CT in diagnosing lymphomas and to characterize the influence of FAP and glycolytic markers on tracer uptake by involved lesions. <b>Methods:</b> Participants with different lymphoma subtypes who were prospectively recruited from May 2020 to December 2021 underwent <sup>68</sup>Ga-FAPI and <sup>18</sup>F-FDG PET/CT. Immunohistochemistry was performed to evaluate FAP, hexokinase 2, and glucose transporter 1 (GLUT1) expression, and the paired-samples <i>t</i> 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. <b>Results:</b> 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. <sup>18</sup>F-FDG PET possessed a higher staging accuracy (98.4%) than <sup>68</sup>Ga‐FAPI PET (86.0%). In 5,980 lymphoma lesions, <sup>18</sup>F-FDG PET/CT detected more nodal (4,624 vs. 2,196) and extranodal (1,304 vs. 845) lesions than <sup>68</sup>Ga-FAPI PET/CT. Additionally, 52 <sup>68</sup>Ga-FAPI–positive/<sup>18</sup>F-FDG–negative lesions and 2,939 <sup>68</sup>Ga-FAPI–negative/<sup>18</sup>F-FDG–positive lesions were observed. In many lymphoma subtypes, semiquantitative evaluation revealed no significant differences in SUV<sub>max</sub> or target-to-liver ratios between <sup>68</sup>Ga-FAPI and <sup>18</sup>F-FDG PET/CT (<i>P</i> > 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 <sup>68</sup>Ga-FAPI SUV<sub>max</sub> (<i>r</i> = 0.622, <i>P</i> = 0.001) and <sup>18</sup>F-FDG SUV<sub>max</sub> (<i>r</i> = 0.835, <i>P</i> < 0.001), respectively. <b>Conclusion:</b><sup>68</sup>Ga-FAPI PET/CT was inferior to <sup>18</sup>F-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.