Fluorine-18-labeled somatostatin analogs (SSAs) could represent a valid alternative to the current gold standard gallium-68-labeled SSAs for somatostatin receptor (SSTR) imaging in patients with neuroendocrine tumors (NETs), given their logistical advantages. Recently, 18 F-AlF-NOTAoctreotide ( 18 F-AlF-OC) has emerged as a promising candidate, but a thorough comparison with 68 Ga-DOTA-SSA in large patient groups is needed. This prospective, multicenter trial aims to demonstrate non-inferiority of 18 F-AlF-OC compared with 68 Ga-DOTA-SSA PET in NET patients (ClinicalTrials.gov: NCT04552847).Methods: Seventy-five patients with histologically confirmed NET and a routine clinical 68 Ga-DOTATATE (n=56) or 68 Ga-DOTANOC (n=19) PET, performed within a 3-month interval of the study scan (median: 7 days; range: -30 to +32 days), were included. Patients underwent a wholebody PET, two hours after IV injection of 4 MBq/kg 18 F-AlF-OC. A randomized, blinded consensus read was performed by two experienced readers to count tumor lesions. Following unblinding, the detection ratio (DR) was determined for each scan, i.e. the fraction of lesions detected on a scan compared to the union of lesions of both scans. The differential detection ratio (DDR; difference in DR between 18 F-AlF-OC and 68 Ga-DOTATATE/NOC) per patient was calculated. Tracer uptake was evaluated by comparing SUV max and tumor-to-background ratios (TBRs) in concordant lesions. Results:In total, 4709 different tumor lesions were detected, 3454 with 68 Ga-DOTATATE/NOC and 4278 with 18 F-AlF-OC. The mean DR with 18 F-AlF-OC was significantly higher than with 68 Ga-DOTATATE/NOC (91.1% vs. 75.3%; P<10 -5 ). The resulting mean DDR was 15.8% with a lower margin of the 95% confidence interval (95% CI: 9.6%-22.0%) higher than -15%, the pre-specified boundary for non-inferiority. The mean DDR for the 68 Ga-DOTATATE and 68 Ga-DOTANOC subgroups were 11.8% (95% CI: 4.3-19.3) and 27.5% (95% CI: 17.8-37.1), respectively. The mean DDR for most organs was higher than zero, except for bone lesions (mean DDR -2.8% (95% CI: -17.8-12.2)). No significant differences in mean SUV max were observed (P = 0.067), but mean TBR was significantly higher with 18 F-AlF-OC than with 68 Ga-DOTATATE/NOC (31.7±36.5 vs. 25.1±32.7; P=0.001). Conclusion:18 F-AlF-OC is non-inferior and even superior compared with 68 Ga-DOTATATE/NOC PET in NET patients. This validates 18 F-AlF-OC as an option for clinical practice SSTR PET.

BackgroundSeveral studies have shown that 18F-FDG PET may contribute to the diagnosis of polymyalgia rheumatica (PMR). Previously, we developed a composite PET score called the Leuven score, which was recently adapted to the more concise Leuven/Groningen score by van der Geest et al. The aim of this study is to validate and compare the diagnostic accuracy and cut-off points of both scores in a large cohort of PMR patients.MethodsPatients with a possible clinical diagnosis of PMR and a PET scan prior to the initiation of glucocorticoids between 2003 and 2020 were included retrospectively. The gold standard for the diagnosis of PMR was the judgment of two experienced clinicians after a follow-up of at least 6 months. FDG uptake was scored visually in 12 articular regions (scores 0–2) and a total skeletal score was calculated by summing the individual scores (maximum of 24 for the Leuven score and 14 for the Leuven/Groningen score). Receiver operating characteristic (ROC) analysis and the Youden index were used to determine the diagnostic accuracy and optimal cut-off points.ResultsA total of 162 patients with PMR and 83 control patients were included. Both PET scores showed high diagnostic accuracy in the ROC analysis (area under the curve 0.986 and 0.980, respectively). The Leuven Score provided a sensitivity of 91.4%, specificity of 97.6% and accuracy of 93.5% at its predefined cut-off point of 16. With the newly determined cut-off point of 12 the sensitivity was 98.8%, the specificity 95.2% and the accuracy 97.6%. The Leuven/Groningen score had a sensitivity, specificity and accuracy of 93.2%, 95.2%, and 93.9%, respectively, with the pre-specified cut-off point of 8, and 96.9%, 92.8%, and 95.5% with the optimal cut-off point of 7.ConclusionThe original Leuven score and the simplified Leuven/Groningen score both had excellent diagnostic accuracy. The latter may be easier to apply in clinical practice.

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BackgroundPatients with giant cell arteritis (GCA) have an increased risk of developing aortic aneurysms. Retrospective studies have shown that18F-fluorodeoxyglucose (FDG) uptake in large vessels at diagnosis increases the risk of developing aortic complications during follow-up.ObjectivesTo prospectively evaluate the association between vascular FDG uptake at diagnosis and the evolution of aortic diameter and volume in patients with GCA.MethodsGCA patients who had FDG positron emission tomography (PET) imaging at diagnosis within 3 days of initiation of glucocorticoids and who were prospectively followed for at least 2 years were included. PET scans were visually scored (0-3) at 7 vascular areas and a total vascular score (TVS) was calculated, ranging from 0 to 21. Patients underwent a computed tomography (CT) scan at diagnosis and yearly thereafter for a maximum of 10 years. The association between vascular FDG uptake and aortic diameter and volume was estimated by linear mixed effect models with random intercept and slope adjusted for age, sex, cardiovascular risk factors, CT or PET/CT scan and intravenous contrast. The ascending aorta, aortic arch, and descending aorta were considered aneurysmatic when the diameter was ≥45, ≥40, and ≥35 mm, respectively.ResultsHundred patients (mean age 70 years, 68% females) were included, of which 74 patients had FDG uptake ≥2 in any large vessel, 60 in the thoracic aorta and 49 in the abdominal aorta. Median follow-up was 80 months (IQR 47-110). The increase in ascending and descending aortic diameter and in thoracic aortic volume was higher in patients with vascular FDG uptake ≥2 compared to those without (Table 1). This increase was also significantly associated with TVS (Figure 1). FDG uptake was not associated with an increase in abdominal aortic diameter nor volume. Thoracic aortic aneurysms were more frequently observed in patients with thoracic aortic FDG uptake (27% versus 10%, aOR 6.6, 95%-CI 1.8-31.0, p=0.009) with a median time since diagnosis of 40 months (IQR 18-61). Two patients with high TVS (15 and 16) needed surgery for thoracic aortic aneurysm.ConclusionThoracic aortic FDG uptake at diagnosis is an independent risk factor for developing thoracic aortic aneurysm in GCA patients. Higher TVS was associated with greater yearly increase in thoracic aortic volume and diameter. Follow-up of aortic dimensions may be necessary in these patients.Table 1.Evolution of the aortic diameter (in mm) and volume (in cm³) per year in patients with (PET positive) and without (PET negative) vascular FDG uptake ≥2FDG uptake ≥2 in any large vesselRegression coefficient (95% CI)p-valuePET negativePET positiveVolume of thoracic aorta2.40 (-0.40 – 5.21)6.80 (5.09 – 8.53)0.008Volume of abdominal aorta0.28 (-0.48 – 1.04)0.12 (-0.33 – 0.57)0.72Diameter of thoracic aorta ◦ Ascending aorta0.10 (-0.10 – 0.30)0.41 (0.29 – 0.53)0.009 ◦ Aortic arch0.21 (0.05 – 0.37)0.35 (0.25 – 0.45)0.14 ◦ Descending aorta0.11 (-0.06 – 0.27)0.34 (0.24 – 0.44)0.01Diameter of abdominal aorta ◦ Suprarenal aorta0.07 (-0.04 – 0.17)0.11 (0.04 – 0.17)0.51 ◦ Juxtarenal aorta0.14 (0.03 – 0.25)0.14 (0.07 – 0.21)0.98 ◦ Infrarenal aorta0.15 (0.07 – 0.23)0.08 (0.03 – 0.12)0.11FDG uptake ≥2 in thoracic aortaRegression coefficient (95% CI)p-valuePET negativePET positiveVolume of thoracic aorta3.13 (0.86 – 5.43)7.32 (5.44 – 9.22)0.005Diameter of thoracic aorta ◦ Ascending aorta0.15 (-0.02 – 0.31)0.45 (0.31 – 0.58)0.005 ◦ Aortic arch0.22 (0.09 – 0.35)0.37 (0.27 – 0.48)0.07 ◦ Descending aorta0.18 (0.05 – 0.32)0.35 (0.23 – 0.46)0.06FDG uptake ≥2 in abdominal aortaRegression coefficient (95% CI)p-valuePET negativePET positiveVolume of abdominal aorta0.08 (-0.45 – 0.61)0.23 (-0.33 – 0.78)0.69Diameter of abdominal aorta ◦ Suprarenal aorta0.07 (-0.00 – 0.14)0.12 (0.05 – 0.20)0.32 ◦ Juxtarenal aorta0.13 (0.05 – 0.20)0.15 (0.07 – 0.23)0.70 ◦ Infrarenal aorta0.12 (0.07 – 0.18)0.06 (0.00 – 0.12)0.12Figure 1.Association between TVS and (A) volume of thoracic aorta, (B) diameter of ascending aorta and (C) diameter of descending aortaREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Letters to the EditorsClinical implications of fever at diagnosis in polymyalgia rheumatica: an age-and sex-matched case control study of 120 patients. Reply to Milchert et al. and Manzo et al.