Fibroblast activation protein expression in tumour microenvironment is crucial in differentiation and survival prediction of recurrent gliomas: a head-to-head comparison of 68Ga-FAPI-04 and 18F-FET in PET/CT imaging

Background —The accurate differentiation of recurrent glioma from treatment-related changes, such as pseudoprogression or radiation necrosis, is crucial for treatment planning and remains a critical challenge. Fibroblast activation protein (FAP) expressed by cancer-associated fibroblasts can be targeted with PET tracers for in vivo visualization and quantification. This research aims to evaluate the diagnostic and survival predictive efficacy of FAP expression in possible recurrent glioma patients with a head-to-head comparison of [gallium-68] FAP inhibitor-04 and [fluoride-18] fluoroethyl-L-tyrosine PET/CT imaging. 30 post-treatment glioma patients with possible recurrent signs under regular MRI follow-up were enrolled. PET-based semiquantitative parameters and clinical factors were obtained for analysis. Results —Univariate logistic regression indicated the initial pathological diagnosis has a borderline differential efficacy (P=0.053). In Multivariate logistic regression analysis of PET-based semiquantitative parameters, MTV _FAPI :MTV _FET ratio showed borderline differential efficacy (P=0.094). When including PET parameters and initial pathological diagnosis, the effectiveness of initial pathological diagnosis was significant (P = 0.045), and the MTV _FAPI :MTV _FET ratio enhanced the area under the receiver operating characteristic curve (AUC) (P=0.040). When the initial diagnosis was replaced with the WHO grade, both the MTV _FAPI :MTV _FET ratio (P=0.081) and the WHO grade (P=0.086) showed borderline efficacy, while the MTV _FAPI :MTV _FET ratio improved the AUC (P=0.016). After factoring in age and gender, the initial pathological diagnosis remained significant (P=0.038). Three parameters, including gender (P=0.057), MTV _FAPI :MTV _FET ratio (P=0.076), and MTV-FAPI (P=0.093), demonstrated borderline efficacy, with the MTV _FAPI :MTV _FET ratio enhancing the AUC (P=0.039). Similarly, after replacing the initial pathological diagnosis with the initial WHO grade, the initial WHO grade (P=0.072), MTV _FAPI :MTV _FET ratio (P=0.079), and gender (P=0.089) presented with borderline differential efficacy, and the MTV _FAPI :MTV _FET ratio similarly significantly enhanced the AUC of the model (P=0.046). The survival analysis indicated that MTV-FAPI significantly affects the overall survival (P=0.027, hazard ratio=1.103, 95% CI: 1.011-1.204). Conclusions —This head-to-head study illustrated FAP expression volume percentage of the post-treatment glioma patients has potential in the differentiation between glioma recurrence and treatment-related changes. Glioma FAP expression volume is an independent risk factor that could significantly influence the overall survival of this glioma cohort.