Distinguishing Benign and Malignant Findings on [(68) Ga]-FAPI PET/CT Based on Quantitative SUV Measurements

AIM/PURPOSE: Fibroblast activation protein (FAP) is overexpressed by cancer-associated fibroblasts. However, activated fibroblasts have been shown to play a significant role also in certain benign conditions such as wound healing or chronic inflammation. Therefore, the current study aimed to identify whether FAPI uptake might differ between malignant lesions and benign conditions. MATERIAL AND METHODS: We retrospectively analyzed 155 patients with various cancer types who received [(68) Ga]-FAPI-04/02-PET/CT between July 2017 and March 2020. SUV(max), SUV(mean), and lesion-to-background ratios (LBR) of FAPI uptake were measured in benign processes compared to malignant lesions (primary and/or 2 exemplary metastases). In addition, receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive capabilities of semiquantitative PET/CT parameters. Furthermore, the sensitivity, specificity, optimal cutoff value, and 95% confidence interval (CI) were determined for each parameter. RESULTS: Benign lesions exhibited significantly lower FAPI uptake compared to malignant lesions (mean SUV(max) benign vs. malignant: 4.2 vs. 10.6; p < 0.001). In ROC analysis, cutoff values of these lesions (benign vs. malignant) were established based on SUV(max), SUV(mean), and LBR. The SUV(max) cutoff value for all lesions was 5.5 and the corresponding sensitivity, specificity, accuracy, and AUC were 78.8%, 85.1%, 82.0%, and 0.89%, respectively. CONCLUSION: Our aim was to systematically analyze the pattern of FAPI uptake in benign and malignant processes. This investigation demonstrates that FAPI uptake might be useful to differentiate malignant and benign findings due to different patho-physiological origins. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11307-022-01759-5.