Introduction: Fibroblast activation protein (FAP) is overexpressed in several solid tumors and therefore represents an attractive target for radiotheranostic applications. Recent investigations demonstrated rapid and high uptake of small-molecule inhibitors of FAP ( 68 Ga-FAPI-46) for PET imaging. Here, we report our initial experience in terms of feasibility and safety of 90 Y-labelled FAPI-46 ( 90 Y-FAPI-46) for radioligand therapy (RLT) of extensively pretreated patients with solid tumors. Methods: Patients were considered for 90 Y-FAPI-46 therapy in case of (a) exhaustion of all approved therapies based on multidisciplinary tumor board decision and (b) high FAP expression, defined as SUVmax ≥ 10 in more than 50% of all lesions. If tolerated, posttherapeutic 90 Y-FAPI-46 bremsstrahlung scintigraphy was performed to visually confirm systemic distribution and focal tumor uptake, and 90 Y-FAPI-46 PET scans at multiple timepoints were performed to determine absorbed dose. Blood-based dosimetry was used to determine bone-marrow absorbed dose. Adverse Events were graded using CTCAE v.5.0. Results: Nine patients with either metastatic soft tissue or bone sarcoma (N = 6) and pancreatic cancer (N = 3) were treated between June 2020 and March 2021. Patients received a median of 3.8 (IQR 3.25-5.40) GBq for the first cycle and three patients received subsequent cycles with a median of 7.4 (IQR 7.3-7-5) GBq. Post-therapy 90 Y-FAPI-46 bremsstrahlung scintigraphy demonstrated sufficient 90 Y-FAPI-46 uptake in tumor lesions in 7 of 9 patients (78%). Mean absorbed dose was 0.52 Gy/GBq (IQR 0.41-0.65) in kidney, 0.04 Gy/GBq (IQR 0.03-0.06) in bone marrow and below 0.26 Gy/GBq in the lung and liver. Measured tumor lesions received up to 2.28 Gy/GBq (median 1.28Gy/GBq). Hematologic G3/G4 toxicities were noted in four patients (44%), of which

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. 68 Ga-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 68 Ga-FAPI-PET were eligible for enrollment into the FAPI-PET observational trial. Of these patients, 43 patients also underwent 18 F-Fluordesoxyglucose PET (FDG). The primary study endpoint was the association of 68 Ga-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.

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Treatment of a defined subset of patients with outpatient intravenous ceftriaxone was safe and effective. Signs of sepsis were the only factor significantly associated with bloodstream infection. This study provides a baseline for future prospective studies assessing the safety of withholding antibiotics in this subset of patients.

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 SUVmax 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 SUVmax was observed (average ∆SUVmax: + 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.