Introduction: Fibroblast activation protein inhibitor positron emission tomography (FAPI-PET) is a new tool in the diagnostic workup of cancer. With growing volume of applications pitfalls and common findings need to be considered for Ga-68-FAPI-PET image interpretation. The aim of this study was to summarize common findings and report pitfalls in Ga-68-FAPI-PET. Methods and materials: 91 patients underwent whole-body PET/CT with either FAPI-04 (N = 25) or FAPI-46 (N = 66). Findings were rated in a consensus session of two experienced readers. Pitfalls and common findings were defined as focal or localized uptake above background and categorized as unspecific / non-malignant and grouped into degenerative, muscular, scarring / wound-healing, uterine, mammary glands and head-and-neck findings. Frequency of findings was reported on a per-patient and per-group basis and SUV_max, SUVmean and SUVpeak was measured. Results: Non-tumor specific tracer uptake was found in 81.3 % of patients. The most frequent finding was tracer uptake in degenerative lesions (51.6%) with mean SUV_max 7.7 ± 2.9 and head-and-neck (45.1%) findings. Except for salivary glands, the uptake values did not differ between 10 and 60 min p.i. in most findings. Uterine uptake was found in most women (66.7%) with mean SUV_max 12.2 ± 7.3 and uptake correlated negatively with age (SUV_max r = -0.6, p<0.01; SUVpeak r = -0.57, p<0.01; SUVmean r = -0.58, p<0.01). Conclusion: Pitfalls include non-tumor specific Ga-68-FAPI uptake in degenerative lesions, muscle, head-and-neck, scarring, mammary glands or uterus. Here we summarize findings to inform readers at centers introducing Ga-68-FAPI-PET to avoid common mistakes.

Introduction: Bone and soft tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblast. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radio-labelled FAP-Inhibitors (e.g. ⁶⁸Ga-FAPI46) have shown high tumor uptake in positron emission tomography (PET) in sarcoma patients. Here we report endpoints of the FAPI-PET prospective observational trial. Methods: Forty-seven patients with bone or soft tissue sarcomas undergoing clinical ⁶⁸Ga-FAPI-PET were eligible for enrollment into the FAPI-PET observational trial. Of these patients, 43 patients also underwent ¹⁸F-Fluordesoxyglucose PET (FDG). The primary study endpoint was the association of ⁶⁸Ga-FAPI-PET uptake intensity and histopathological FAP-expression analyzed with Spearman’s r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by two blinded readers. Results: Primary endpoint was met and the association between FAPI-PET uptake intensity and histopathological FAP-expression was significant (Spearman’s r = 0.43; P = 0.03). By histopathological validation PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET positive resulting in an SE of 0.96 (95%CI, 0.82-1.00) on a per-patient and 0.94 (95%CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in FAPI- and FDG-PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients FAPI-PET resulted in an upstaging compared to FDG-PET. FAPI-PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss kappa: primary κ = 0.78; local nodal κ = 0.54; distant nodal κ = 0.91; lung κ = 0.86; bone κ = 0.69 and other κ = 0.65). Clinical management changed in 13 (30%) patients after FAPI-PET. Conclusion: We confirm an association of tumoral FAPI-PET uptake intensity and histopathological FAP expression in sarcoma patients. Further, using blinded reads and independent histopathological validation we report high PPV and sensitivity of FAPI-PET for sarcoma staging.

A novel radiofluorination procedure using only precursor and [¹⁸F]fluoride without the need for azeotropic drying, base and other ingredients was developed.

Aims: The aim of this retrospective analysis was to examine the pattern of cardiac ⁶⁸Ga-fibroblast-activation protein-α inhibitor (FAPI) uptake in patients after acute myocardial infarction (AMI) using PET and to investigate its association with results of coronary angiography. We correlated FAPI uptake with biomarkers of myocardial damage including left ventricular function. Methods and Results: A cohort of 10 patients with no history of coronary artery disease underwent PET 18 ± 20.6 days after AMI (ST-segment elevation myocardial infarction [n = 5] and non–ST-segment elevation infarction [n = 5]), respectively. SUVmax, SUVmean, and SUVpeak of localized tracer uptake were calculated; tracer uptake volume was reported as fibroblast activation volume (FAV), with imaging data being correlated with clinical parameters. Focal FAPI uptake was observed in all patients. Average uptake at 10 minutes postinjection was 8.9 ± 4.4 (SUVmax), 7.6 ± 4.0 (SUVpeak), and 5.3 ± 2.8 (SUVmean), respectively. Affected myocardium showed a partial to complete match between tracer uptake and confirmed culprit lesion by coronary angiography in 44.4% and 55.6% of patients, respectively. A strong correlation between FAV and peak creatine kinase level (r = 0.90, P < 0.01) and inverse correlation of FAV with left ventricular function (r = −0.69, P < 0.05) was observed. Conclusions: This analysis demonstrates in vivo visualization of fibroblast activation after AMI. The uptake area showed a very good agreement with the affected coronary territory. A strong correlation of the de novo established parameter FAV with left ventricular function and peak creatine kinase was observed. This imaging modality may provide important insights into mechanisms of structural remodeling after AMI at an early stage.

Introduction: Positron emission tomography (PET) using small ligands of the fibroblast activation protein (FAP) was recently introduced. However, optimal uptake time has not been defined yet. Here, we systematically compare early (~ 10 min p.i.) and late (~ 60 min p.i.) FAPI-46 imaging in patients with various types of cancer. Methods: This is a retrospective single-institutional study. Imaging was performed at the Essen University Hospital, Germany. A total of 69 patients who underwent dual time-point imaging for either restaging (n = 52, 75%) or staging (n = 17, 25%) of cancer were included. Patients underwent PET with two acquisitions: early (mean 11 min, SD 4) and late (mean 66 min, SD 9). Mean injected activity was 148 MBq (SD 33). Results: In total, 400 lesions were detected in 69 patients. Two of 400 (0.5%) lesions were only seen in early time-point imaging but not in late time-point imaging. On a per-patient level, there was no significant difference between SUV_max of hottest tumor lesions (Wilcoxon: P = 0.73). Organ uptake demonstrated significant early to late decrease in SUVmean (average ∆SUVmean: − 0.48, − 0.14, − 0.27 for gluteus, liver, and mediastinum, respectively; Wilcoxon: P < 0.001). On a per-lesion basis, a slight increase of SUV_max was observed (average ∆SUV_max: + 0.4, Wilcoxon: P = 0.03). Conclusion: In conclusion, early (~ 10 min p.i.) versus late (~ 60 min p.i.) FAPI-46 imaging resulted in equivalent lesion uptake and tumor detection. For improved feasibility and scan volume, we implement early FAPI-46 PET in future clinical and research protocols.