Detecting Fibroblast Activation Proteins in Lymphoma Using ⁶⁸Ga-FAPI PET/CT

Cancer-associated fibroblasts that overexpress fibroblast activation protein (FAP) are enriched in many epithelial carcinomas and in hematologic neoplasms. PET/CT with radiolabeled FAP inhibitor (FAPI) is a new diagnostic tool for visualizing the tumor stroma. This prospective study aimed to profile FAPs in different subtypes of lymphomas and explore the potential utility of ⁶⁸Ga-FAPI PET/CT in lymphomas. Methods: In this prospective study, we recruited 73 lymphoma patients who underwent ⁶⁸Ga-FAPI PET/CT and recorded and measured semiquantitative parameters and ratios of their scan results. FAPI expression was assessed by immunochemistry in samples obtained from 22 of the lymphoma patients. Results: We evaluated 11 patients with Hodgkin lymphoma and 62 with non-Hodgkin lymphoma (NHL). Significantly elevated FAP uptake was observed in Hodgkin lymphoma lesions, correlating with the intensity of FAP immunostaining (score, 3+). A positive association was found between the corresponding clinical classification of NHL and the ⁶⁸Ga-FAPI uptake activity of the lesion. Aggressive NHL lesions, with moderate to strong FAP immunostaining (score, 2+ to 3+), exhibited intense to moderate ⁶⁸Ga-FAPI uptake. Indolent NHL lesions showed weak FAP staining and mild to moderate ⁶⁸Ga-FAPI uptake. No statistically significant correlation emerged between the sum of the product of the diameters and the corresponding SUV_max (P = 0.424). The tumor-to-liver ratios were 6.26 ± 4.17 in indolent NHL and more than 9 in other subtypes. Conclusion:⁶⁸Ga-FAPI imaging can be used to detect FAP expression in lymphoma lesions and may be an alternate method for characterizing lymphoma profiles.