Exploratory Evaluation of TBR Thresholds for Arterial [18F]F-FAPI-74 PET/CT

Background/Objectives: Fibroblast activation protein inhibitor (FAPI)-directed PET/CT has emerged as a promising approach for non-invasive assessment of arterial wall pathology. While a target-to-background ratio (TBR) threshold of 1.6 has previously been applied for vascular [68Ga]Ga-FAPI-04 imaging, no established threshold exists for [18F]F-FAPI-74. Given differences in physical imaging characteristics and tracer kinetics, this study systematically evaluated candidate TBR thresholds for arterial [18F]F-FAPI-74 uptake, using CT-derived calcification as a morphological comparator. Methods: Seventy-two oncological patients undergoing [18F]F-FAPI-74 PET/CT were retrospectively analyzed. Six vascular territories were assessed for focal vessel wall-associated tracer uptake and CT-derived calcification. Three primary candidate TBR thresholds (1.2, 1.4, and 1.6) were selected for focused comparison, while complementary thresholds from 1.0 to 2.0 in increments of 0.1 were assessed descriptively. For each threshold, the number of FAPI-positive sites, proportion of FAPI-positive sites with concomitant calcification, and proportion of calcification-positive sites with concomitant FAPI uptake were determined. All co-localization measures were interpreted as descriptive morphological comparisons and not as measures of biological FAP expression, diagnostic sensitivity, or diagnostic accuracy. Results: Focal arterial uptake was detected in 69/72 patients (95.8%) at a TBR threshold of 1.2, 61/72 (84.7%) at 1.4 and 38/72 (52.8%) at 1.6. The corresponding numbers of FAPI-positive sites were 896, 452 and 220. Among the three primary candidate thresholds, the proportion of FAPI-positive sites with concomitant calcification remained broadly comparable (66.7%, 60.2%, and 68.2%, respectively), whereas the proportion of calcification-positive sites with concomitant FAPI uptake decreased from 23.4% at a TBR threshold of 1.2 to 10.7% at 1.4 and 5.9% at 1.6. Across the broader TBR range, lower thresholds, including 1.0 and 1.1, yielded greater site detection and numerically higher calcification co-localization than the TBR threshold of 1.2, and no unique empirical optimum was identified. Conclusions: A TBR threshold of 1.2 represents a pragmatic candidate threshold within the predefined primary range rather than an empirically optimized cut-off. Prospective validation in dedicated cardiovascular cohorts using standardized imaging protocols and biological reference standards is required before a generally applicable threshold for arterial [18F]F-FAPI-74 imaging can be established.