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Objective: Surgical resection is the therapy of choice in head and neck paraganglioma but is associated with considerable morbidity. For treatment of inoperable or progressive disease, less aggressive adjuvant options are warranted. This study assessed effectiveness and safety of peptide receptor radionuclide therapy (PRRT) with lutetium-177-DOTATATE for head and neck paraganglioma with emphasis on response assessment., Methods: A retrospective analysis of 7 patients with head and neck paraganglioma treated with PPRT between May 2014 and October 2016 was performed. Three patients had jugulotympanic paraganglioma, 3 patients had carotid body tumors, and 1 patient had a combination of both. Patients underwent PRRT after discussion in the local tumor board regarding progressive disease, inoperability, or lack of other adjuvant options. All patients underwent 3-5 cycles of PRRT. Treatment response was evaluated by gallium-68-DOTATATE positron emission tomography/computed tomography and contrast-enhanced computed tomography or magnetic resonance imaging. Outcome measures were two-dimensional tumor diameters and total tumor volumes., Results: Median patient age was 60 years (interquartile range: 14-84 years). All patients had stable disease at posttherapy assessment. Decreasing tumor volumes were found in 4 patients. Clinical symptoms improved in 2 patients. No progression or adverse events occurred during a median follow-up of 39 months (interquartile range: 35-47 months)., Conclusions: Somatostatin receptor-targeted therapy using lutetium-177-DOTATATE shows promising effectiveness with a high safety profile. Patients in whom surgical morbidity outweighs oncologic benefit should be informed about PRRT as a treatment option., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder. The contribution of the immune system to its pathogenesis remains incompletely understood. In this study, we performed comprehensive immune cell profiling in the cerebrospinal fluid (CSF) and peripheral blood of patients with FTD. Thirty-two patients with behavioral variant frontotemporal dementia and 25 patients with primary progressive aphasia were included and compared to 14 healthy elderly controls. All patients underwent neuropsychological examination, magnetic resonance imaging, voxel-based diffusion tensor imaging, and peripheral blood and CSF immune cell profiling by multiparameter flow cytometry. The percentage of CSF monocytes was significantly increased specifically in patients with primary progressive aphasia. The proportion of monocytes in the CSF of the total FTD patient group directly correlated with semantic language impairment and microstructural temporal lesions. Increased intrathecal numbers of monocytes suggest a specific response of the innate immune system in a subset of patients with FTD. The findings are of clinical relevance since monocyte levels in the CSF were correlated with typical neuropsychological deficits and microstructural patterns of temporal degeneration., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In the HD15 trial of the German Hodgkin Study Group, the negative predictive value (NPV) of positron emission tomography (PET) using [(18)F]-fluorodeoxyglucose in advanced-stage Hodgkin lymphoma (HL) was evaluated. A total of 817 patients were enrolled and randomly assigned to receive BEACOPP-based chemotherapy. After completion of chemotherapy, residual disease measuring more than or equal to 2.5 cm in diameter was assessed by PET in 311 patients. The NPV of PET was defined as the proportion of PET(-) patients without progression, relapse, or irradiation within 12 months after PET review panel. The progression-free survival was 96% for PET(-) patients (95% confidence interval [CI], 94%-99%) and 86% for PET(+) patients (95% CI, 78%-95%, P = .011). The NPV for PET in this analysis was 94% (95% CI, 91%-97%). Thus, consolidation radiotherapy can be omitted in PET(-) patients with residual disease without increasing the risk for progression or early relapse compared with patients in complete remission. The impact of this finding on the overall survival at 5 years must be awaited. Until then, response adapted therapy guided by PET for HL patients seems to be a promising approach that should be further evaluated in clinical trials. This trial is registered at http://isrctn.org study as #ISRCTN32443041.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a promising tracer for PET that has demonstrated convincing results especially in the diagnostics of brain tumors. In contrast to other radiolabeled amino acids, it can be produced with high efficiency and distributed in a satellite concept like the widely used 2-[18F]fluoro-2-deoxy-D-glucose. Although FET is not incorporated into proteins, it shows high uptake in cerebral gliomas and in extracranial squamous cell carcinomas owing to increased transport. The tracer exhibits high in vivo stability, low uptake in inflammatory tissue and suitable uptake kinetics for clinical imaging, which indicates that it may become a new standard tracer for PET. In this article, the present knowledge on the uptake mechanisms and the clinical applications of FET are reviewed and the clinical perspectives are discussed.

The radiolabelled amino acid 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) is a promising tool for the diagnosis and monitoring of brain tumors using single-photon emission tomography (SPECT). However, little is known about the precise kinetics of [(123)I]IMT uptake in human glioma cells. The kinetic analysis of [(123)I]IMT transport in human GOS3 glioma cells yielded a high-affinity apparent Michaelis constant (K(m) = 20.1 +/- 1.5 microM). The maximum transport velocity (V(max)) amounted to 34.8 +/- 1.9 nmol/mg protein/10 min. Competitive inhibition experiments revealed that [(123)I]IMT transport is mediated principally by the sodium-independent system L.

The distribution of nicotinic and muscarinic cholinergic receptors in the human brain in vivo has been successfully characterized using radiolabeled tracers and emission tomography. The effect of acetylcholine release into the synaptic cleft on receptor binding of these tracers has not yet been investigated. The present study examined the influence of acetylcholine on binding of 4-[125I]iododexetimide to muscarinic cholinergic receptors of porcine brain synaptosomes in vitro. 4-Iododexetimide is a subtype-unspecific muscarinic receptor antagonist with high affinity. Acetylcholine competed with 4-[125I]iododexetimide in a dose-dependent manner. A concentration of 500 microM acetylcholine inhibited 50% of total specific 4-[125I]iododexetimide binding to synaptosomes when both substances were given simultaneously. An 800 microM acetylcholine solution reduced total specific 4-[125I]iododexetimide binding by about 35%, when acetylcholine was given 60 min after incubation of synaptosomes with 4-[125I]iododexetimide. Variations in the synaptic acetylcholine concentration might influence muscarinic cholinergic receptor imaging in vivo using 4-[123I]iododexetimide. Conversely, 4-[123I]iododexetimide might be an appropriate molecule to investigate alterations of acetylcholine release into the synaptic cleft in vivo using single photon emission computed tomography.

To test the hypothesis that cerebral vasomotor reactivity (CVMR) is significantly more reduced in patients with hemispheric low-flow infarctions than in brain infarctions due to arterio-arterial embolism, a series of 64 consecutive patients with internal carotid artery occlusions were studied. CVMR was calculated from relative changes of blood flow velocity within the middle cerebral artery (MCA) measured by transcranial Doppler ultrasonography (TCD) during hypo- and hypercapnia. The configuration of the circle of Willis (COW) was also determined by TCD using common carotid artery compression tests. Anterior, posterior or ophthalmic artery collateral flow, and absence or combinations of these, were differentiated. CT scans were categorized as showing either no infarction (group I; n = 20) or territorial (group II; n = 28), or low-flow infarctions (group III; n = 16). As compared to normal, CVMR was significantly reduced but equal in groups I and II, however, even more reduced in group III. CVMR was lowest, and low-flow infarctions were most frequent in patients whose collateral hemispheric blood supply was from the ophthalmic artery as opposed to patients with a complete or nearly complete COW. Our findings indicate that low-flow infarctions in extracranial ICA occlusions represent brain damage due to a critical reduction in cerebral perfusion pressure, as opposed to thromboembolically induced lesions. The configuration of the COW seems to play the key role. Our findings also support the view that the pattern of hemispheric infarction seen on CT indicates the pathogenesis of stroke.