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

Abstract

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. SUVmax, SUVmean, 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 SUVmax 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 SUVmax, SUVmean, and LBR. The SUVmax 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.

The Role of Fibroblast Activation Protein Inhibitor Positron Emission Tomography in Inflammatory and Infectious Diseases: An Updated Systematic Review

“…Among them, 190 records were excluded using the previous eligibility criteria (66 because of duplicate records, 30 because of the field of interest, 18 because of reviews/editorials, 72 as case series or case reports, and 4 as preclinical studies). Finally, 21 articles were considered worthy of inclusion in the systematic review (qualitative synthesis) [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. No additional records were added after screening the references of the eligible studies.…”

“…Most research were performed in China ( n = 12), followed by Germany ( n = 6) and Austria ( n = 2). Thirteen studies were conducted with a retrospective design [ 12 , 14 , 15 , 16 , 17 , 18 , 21 , 22 , 23 , 26 , 27 , 30 , 31 ], whereas the remaining eight were prospective. All the studies included in this systematic review were monocentric.…”

“…Lung infectious/inflammatory diseases were the most common conditions investigated in six papers [ 12 , 14 , 16 , 23 , 24 , 26 ] and 200 patients; bone and joint diseases in two papers [ 18 , 22 ], for a total of 185 patients; IgG4-Related disease (IgG4-RD) in two papers [ 29 , 32 ], for a total of 53 patients; and Crohn’s disease in two papers [ 15 , 20 ], for a total of 30 patients. In three articles [ 13 , 21 , 30 ], several mixed benign conditions, including infectious and inflammatory diseases, were also investigated. In the remaining articles, single diseases were studied, such as thyroiditis [ 28 ], myocarditis [ 27 ], systemic sclerosis [ 17 ], rheumatoid arthritis [ 19 ], light-chain cardiac amyloidosis [ 25 ], and renal fibrosis [ 31 ].…”

“…As shown in Table 2 , the index test features were very heterogeneous. Most studies administrated [ 68 Ga]Ga-DOTA-FAPI-04 [ 13 , 15 , 16 , 17 , 18 , 19 , 22 , 25 , 26 , 28 , 29 , 30 , 31 , 32 ], two studies [ 68 Ga]Ga-DOTA-FAPI-46 [ 23 , 24 ], one study [ 18 F]AlF-NOTA-FAPI-04 [ 14 ], one study [ 68 Ga]Ga-DATA5m.SA.FAPI [ 20 ], and one study [ 18 F]-FAPI-74 [ 12 ]; one study used both [ 68 Ga]Ga-DOTA-FAPI-04 and [ 68 Ga]Ga-DOTA-FAPI-02 [ 21 ]; and one paper did not note the radiopharmaceutical form of radiolabeled FAPI in the text [ 27 ]. The radiotracer activity injected was very heterogeneous.…”

Non-tumoral uptake of 68Ga-FAPI-04 PET: A retrospective study

“…Physiological uptake refers to the slightly elevated uptake of 68 Ga-FAPI-04 in generally normal tissues, which usually show no abnormal changes on other imaging modalities ( 20 , 21 ). Benign uptake refers to inflammation, fibrosis, benign tumors, and other non-malignant tumor regions that may be abnormal on other imaging modalities ( 16 , 22 ). For any differences in opinion, a consensus was reached by discussion together.…”