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Background: Cyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine. Aim: To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH). Methods: Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN. Results: In total, 42 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 32 of them in Germany, 4 in Austria and 6 in Switzerland. Two thirds of the cyclotrons reported (67%) are operated by universities, university hospitals or research institutions close to a university hospital, less by/in cooperation with industrial partners (29%) or a non-academic clinic/ PET-center (5%). Most of the cyclotrons (88%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging. Discussion: The data presented provide an academically-updated overview of the medical cyclotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medicine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cycl

Background: Alterations of hypothalamic–pituitary–adrenal (HPA) axis activity and serotonergic signaling are implicated in the pathogenesis of human obesity and may contribute to its metabolic and mental complications. The association of these systems has not been investigated in human obesity. Objective: To investigate the relation of HPA responsiveness and serotonin transporter (5-HTT) availability in otherwise healthy individuals with obesity class II or III (OB) compared to non-obesity controls (NO). Study participants: Twenty-eight OB (21 females; age 36.6 10.6 years; body mass index (BMI) 41.2 5.1 kg/m2) were compared to 12 healthy NO (8 females; age 35.8 7.4 years; BMI 22.4 2.3 kg/m2), matched for age and sex. Methods: HPA axis responsiveness was investigated using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test, and curve indicators were derived for cortisol and adrenocorticotropic hormone (ACTH). The 5-HTT selective tracer [11C]DASB was applied, and parametric images of the binding potentials (BPND) were calculated using the multilinear reference tissue model and evaluated by atlas-based volume of interest (VOI) analysis. The self-questionnaires of behavioral inhibition system/behavioral activation system (BIS/BAS) with subscales drive, fun-seeking and reward were assessed. Results: OB showed significant positive correlations of ACTH curve parameters with overall 5-HTT BPND (ACTHAUC: r = 0.39, p = 0.04) and 5-HTT BPND of the caudate nucleus (ACTHAUC: r = 0.54, p = 0.003). In NO, cortisol indicators correlated significantly with BPND in the hippocampus (cortisolAUC: r = 0.59, p = 0.04). In OB, BAS reward was inversely associated with the ACTHAUC (r = 0.49, p = 0.009). Conclusion: The present study supports a serotonergic-neuroendocrine association, which regionally differs between OB and NO. In OB, areas processing emotion and reward seem to be in-volved. The finding of a serotonergic HPA correlation may have implications for other

Background: The role of the norepinephrine transporter (NET) has received increased focus in recent studies on the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). The predictive value for pharmacological treatment and its link to other health or social limitations has been little-studied. This follow-up research on adult patients with ADHD aimed to explore whether the therapy response and health and social impairments depend on baseline individual NET availability. Methods: Data were collected from 10 patients on personal, family and professional situations, mental and physical health and treatments received after baseline via online and telephone surveys and were compared to baseline data to evaluate treatment-related changes. Results: The majority of our ADHD patients did not show therapy responses but showed improvements due to pharmacological treatment. There was no evidence of relationships between pre-treatment NET availability and therapy response or health/social limitations. Conclusions: Pharmacological monotherapy was insufficient to promote symptom remission, especially for participants with extreme insufficiency in NET availability, but improved outcomes in academic and social functioning. Psychotherapy should be considered as an add-on to the standard treatment approach due to its positive outcome in reducing social limitations. The prognostic value of individual NET availability in predicting the response to therapy needs further studies with large sample sizes

Purpose Dynamic 60-min positron emission tomography (PET) imaging with the novel tau radiotracer [F-18]PI-2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). This study investigated if truncated acquisition and static time windows can be used for [F-18]PI-2620 tau-PET imaging of PSP. Methods Thirty-seven patients with PSP Richardson syndrome (PSP-RS) were evaluated together with ten HCs. [F-18]PI-2620 PET was performed by a dynamic 60-min scan. Distribution volume ratios (DVRs) were calculated using full and truncated scan durations (0-60, 0-50, 0-40, 0-30, and 0-20 min p.i.). Standardized uptake value ratios (SUVrs) were obtained 20-40, 30-50, and 40-60 min p.i.. All DVR and SUVr data were compared with regard to their potential to discriminate patients with PSP-RS from HCs in predefined subcortical and cortical target regions (effect size, area under the curve (AUC), multi-region classifier). Results 0-50 and 0-40 DVR showed equivalent effect sizes as 0-60 DVR (averaged Cohen's d: 1.22 and 1.16 vs. 1.26), whereas the performance dropped for 0-30 or 0-20 DVR. The 20-40 SUVr indicated the best performance of all static acquisition windows (averaged Cohen's d: 0.99). The globus pallidus internus discriminated patients with PSP-RS and HCs at a similarly high level for 0-60 DVR (AUC: 0.96), 0-40 DVR (AUC: 0.96), and 20-40 SUVr (AUC: 0.94). The multi-region classifier sensitivity of these time windows was consistently 86%. Conclusion Truncated and static imaging windows can be used for [F-18]PI-2620 PET imaging of PSP. 0-40 min dynamic scanning offers the best balance between accuracy and economic scanning.

The novel tau-PET tracer [F-18]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer's disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [F-18]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [F-18]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [F-18]PI-2620-positive clusters (DVR >= 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR30-60) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1(SRTM): 0.92 +/- 0.21 vs. 0.83 +/- 0.10, p = 0.0007), higher efflux (k2(SRTM): 0.17/min +/- 0.21/min vs. 0.06/min +/- 0.07/min, p < 0.0001), lower DVR (1.1 +/- 0.1 vs. 1.4 +/- 0.2, p < 0.0001), lower SUVR30-60 (1.3 +/- 0.2 vs. 1.8 +/- 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope(9-60): 0.006/min +/- 0.007/min vs. 0.016/min +/- 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [F-18]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies.

Background Corticobasal syndrome is associated with cerebral protein aggregates composed of 4-repeat (similar to 50% of cases) or mixed 3-repeat/4-repeat tau isoforms (similar to 25% of cases) or nontauopathies (similar to 25% of cases). Objectives The aim of this single-center study was to investigate the diagnostic value of the tau PET-ligand [F-18]PI-2620 in patients with corticobasal syndrome. Methods Forty-five patients (71.5 +/- 7.6 years) with corticobasal syndrome and 14 age-matched healthy controls underwent [F-18]PI-2620-PET. Beta-amyloid status was determined by cerebral beta-amyloid PET and/or CSF analysis. Subcortical and cortical [F-18]PI-2620 binding was quantitatively and visually compared between beta-amyloid-positive and -negative patients and controls. Regional [F-18]PI-2620 binding was correlated with clinical and demographic data. Results Twenty-four percent (11 of 45) were beta-amyloid-positive. Significantly elevated [F-18]PI-2620 distribution volume ratios were observed in both beta-amyloid-positive and beta-amyloid-negative patients versus controls in the dorsolateral prefrontal cortex and basal ganglia. Cortical [F-18]PI-2620 PET positivity was distinctly higher in beta-amyloid-positive compared with beta-amyloid-negative patients with pronounced involvement of the dorsolateral prefrontal cortex. Semiquantitative analysis of [F-18]PI-2620 PET revealed a sensitivity of 91% for beta-amyloid-positive and of 65% for beta-amyloid-negative cases, which is in excellent agreement with prior clinicopathological data. Regardless of beta-amyloid status, hemispheric lateralization of [F-18]PI-2620 signal reflected contralateral predominance of clinical disease severity. Conclusions Our data indicate a value of [F-18]PI-2620 for evaluating corticobasal syndrome, providing quantitatively and regionally distinct signals in beta-amyloid-positive as well as beta-amyloid-negative corticobasal syndrome. In corticobasal syndrome, [F-18]PI-2620 may potentially