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Abstract Background A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [177Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET/CT scan were included. Patients received two short infusions of ~ 1 GBq [177Lu]Lu-PP-F11N in an interval of ~ 4 weeks with and without Entresto® pretreatment in an open-label, randomized cross-over order. Entresto® was given at a single oral dose, containing 48.6 mg sacubitril. Adverse events were graded and quantitative SPECT/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated. Results Pretreatment with Entresto® showed no additional toxicity and increased the stability of [177Lu]Lu-PP-FF11N in blood significantly (p

Background: We sought to investigate magnetic resonance imaging (MRI) parameters that correspond to vasculitis observed via [18F]FDG positron emission tomography/computed tomography (PET/CT) and ultrasound in patients with large-vessel giant cell arteritis (LV-GCA). Methods: We performed a cross-sectional analysis of patients diagnosed with LV-GCA. Patients were selected if MRI, PET/CT, and vascular ultrasound were performed at the time of LV-GCA diagnosis. Imaging findings in vessel segments (axillary segment per side, thoracic aorta) assessed using at least two methods were compared. Vessel wall thickening, oedema, and contrast agent enhancement were each assessed via MRI. Results: Twelve patients with newly diagnosed LV-GCA were included (seven females, 58%; median age 72.1, IQR 65.5–74.2 years). The MRI results showed mural thickening in 9/24 axillary artery segments. All but 1 segment showed concomitant oedema, and additional contrast enhancement was found in 3/9 segments. In total, 8 of these 9 segments corresponded to vasculitic findings in the respective segments as observed via PET/CT, and 2/9 corresponded to vasculitis in the respective ultrasound images. If MRI was performed more than 6 days after starting prednisone treatment, thickening and oedema were seen in only 1/24 segments, which was also pathologic according to ultrasound findings but not those obtained via PET/CT. Four patients had mural thickening, oedema, and contrast enhancement in the aorta, among whom three patients also had vasculitic findings observed via PET/CT. Isolated mural thickening in one patient corresponded to a negative PET/CT result. Conclusions: In the MRI results, mural thickening due to oedema corresponded to vasculitic PET/CT findings but not vasculitic ultrasound findings. The duration of steroid treatment may reduce the sensitivity of MRI.

AIMS To describe the feasibility and diagnostic accuracy of 18F-FDG positron emission tomography-computed tomography (PET/CT) of the temporal artery compared with temporal artery ultrasound and histology of the temporal artery in patients with suspicion of having giant cell arteritis (GCA). MATERIALS AND METHODS Patients with suspected GCA were included. PET/CT standard uptake value ratios and the compression sign on ultrasound were assessed for the trunk, and parietal and frontal branches of the temporal artery. Temporal artery biopsies were systematically re-assessed, if available. RESULTS In 17/34 patients, GCA was confirmed. Temporal artery PET/CT confirmed vasculitis in 9/17 patients and was negative in all 17 controls. Nineteen of 34 subjects had a temporal artery biopsy, which was positive in 7 patients. Five of these seven were negative in the preceding PET/CT. Ultrasound confirmed vasculitis in 9/17 patients and was negative in 16/17 controls. In 7/17 patients, PET/CT and ultrasound were positive for temporal arteritis. Two patients had positive findings only on temporal artery PET/CT and two patients showed vasculitis only on temporal artery ultrasound. No temporal artery segments

We previously proposed standard uptake value (SUV) ratio-based cut-off values for [18F] fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) for diagnosing giant cell arteritis (GCA) with high diagnostic accuracy. Here we confirm our findings in an independent cohort and report a simplified procedure for using a SUV ratio to diagnose LV-GCA. Patients with suspected GCA were consecutively included. The ‘peak SUV ratio’ was defined in a two-step approach. First, the vessel with the visually brightest radiotracer uptake in the supra-aortic (SA) and in the aorto-iliofemoral (AIF) region was identified. Here, the maximum SUV of the vessel was measured and divided by the mean SUV of the liver (SUVratio). A ratio >1.0 in the SA or >1.3 in the AIF region was scored as vasculitis. The diagnostic accuracy, sensitivity, and specificity of the ‘peak SUV ratio’ in the SA and AIF region was assessed. From 2015 to 2019, 50 patients (24 female, median age 71 years) with suspicion of GCA were included, 28 patients with GCA and 22 patients with exclusion of GCA. Peak SUV had an AUC of 0.91, a sensitivity of 0.89, and a specificity of 0.73 for diagnosing GCA. Peak SUV accuracy of the AIF arteries was lower (AUC 0.81) than of the SA arteries (AUC 0.95). Our SUV ratio cut-off values for diagnosing GCA are consistently valid, also when applied in a time-efficient clinical procedure focusing on the peak SUV ratio. The diagnostic performance of PET/CT in this validation cohort was even higher, compared to the inception cohort (AUC of 0.83).

Background: The clinical presentation of Langerhans cell histiocytosis (LCH) is heterogeneous ranging from single-organ involvement to systemic disease causing substantial morbidity and mortality. We describe an unusual course of severe multisystem LCH with spontaneous remission. Case Presentation: We report on a 45-year-old Caucasian woman with cervical cancer, FIGO stage IVB. Five months after the end of combined radiochemotherapy and brachytherapy, the patient was readmitted because of severe dysuria. Sterile leukocyturia was seen, and cystoscopy revealed only 3 unspecific small mucosal lesions compatible with postradiation cystitis. Incidentally, a computed tomography (CT) scan of the body showed diffuse micronodular and cystic lesions in lungs and hypodense lesions in the liver. Biopsies revealed infiltrations of CD1a and Langerin (CD207)-positive histiocytes in the lung, liver, and bladder. Additionally, positron emission tomography-CT (PET-CT) was compatible with bone involvement. Retrospective analysis revealed that the increase in alkaline phosphatase might have been a surrogate of bone marrow infiltration with osseous activity. Repeated pneumothoraces occurred, and only one course of vinblastine-prednisolone could be applied. Despite ongoing tobacco consumption and without further therapy, PET-CT showed considerable remission 2 months later. However, despite stable remission, documented by serial PET and conventional CT scans, persistent infiltration of the bladder by Langerhans histiocytes could still be demonstrated 17 months later. Unfortunately, cervical cancer recurred and progressed. Conclusion: Multisystem LCH may rapidly occur, may be oligosymptomatic and, even in high-risk cases, remission without specific therapy might occur. Whether alkaline phosphatase might be a surrogate to monitor osseous disease activity has to be further explored.

Historically, giant cell arteritis (GCA) was considered to be synonymous with temporal arteritis. However, the disease spectrum of GCA extends much further, and includes vasculitis of the aorta and its branches with or without involvement of the temporal arteries. Imaging is crucial for the diagnosis and follow-up of GCA patients. Large vessel GCA (LV-GCA) often presents as an inflammatory syndrome and is only detected by imaging modalities such as: colour duplex sonography (CDS), computed tomography (CT) / CT angiography (CTA), magnetic resonance imaging (MRI) or 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) / CT. Deciding which imaging modality to use in different clinical situations remains a matter of debate. CDS and MRI enable assessment of the temporal arteries with a presumably higher sensitivity than histology. In the context of a typical presentation, CDS can replace a biopsy. In about a third of patients, the temporal arteries are not involved, thus PET/CT, MRI, CT, or CDS of larger arteries is needed to diagnose GCA. The sensitivity of all modalities is affected by glucocorticoid therapy. Therefore, without delaying therapy, imaging should be performed within a few days of treatment initiation. The use of PET/CT for the work-up of inflammatory syndromes in the elderly reveals vasculitis in approximately 20% of examined patients and uncover relevant diagnoses in the majority of remaining patients. The aorta should be routinely assessed in all GCA patients at diagnosis and during follow-up. MRA or CTA are best suited to characterise structural damage of larger arteries. The role of imaging in monitoring GCA disease activity still needs to be further defined.