Diagnostic Potential of Supplemental Static and Dynamic Ga-FAPI-46 PET for Primary F-FDG-Negative Pulmonary Lesions.

PET using Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic Ga-FAPI-46 PET in the F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic Ga-FAPI-46 PET in addition to F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUV, SUV, and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters (Ga-FAPI-46 in relation toF-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, , , , and ) were extracted from dynamic Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated Ga-FAPI-46 uptake, higher TBRs, and higher Ga-FAPI-46-to-F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative Ga-FAPI-46-to-F-FDG ratios regarding SUV and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Ga-FAPI-46 PET is a powerful new tool for the assessment of single F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting.