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Biodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[11C]Me-NB1
Lucas Rischka1 na1,
Matej Murgaš1 na1,
Verena Pichler2,3,
Chrysoula Vraka2,
Ivo Rausch4,
Dietmar Winkler1,
Lukas Nics2,
Sazan Rasul2,
Leo Robert Silberbauer1,
Murray Bruce Reed1,
Godber Mathis Godbersen1,
Jakob Unterholzner1,
Patricia Handschuh1,
Gregor Gryglewski1,
Thomas Mindt2,6,7,
Markus Mitterhauser2,6,
Andreas Hahn1,
Simon Mensah Ametamey5,
Wolfgang Wadsak2,8,
Rupert Lanzenberger ORCID: orcid.org/0000-0003-4641-95391 &
Marcus Hacker2
The NMDA receptor (NMDAR) plays a key role in the central nervous system, e.g., for synaptic transmission. While synaptic NMDARs are thought to have protective characteristics, activation of extrasynaptic NMDARs might trigger excitotoxic processes linked to neuropsychiatric disorders. Since extrasynaptic NMDARs are typically GluN2B-enriched, the subunit is an interesting target for drug development and treatment monitoring. Recently, the novel GluN2B-specific PET radioligand (R)-[11C]Me-NB1 was investigated in rodents and for the first time successfully translated to humans. To assess whether (R)-[11C]Me-NB1 is a valuable radioligand for (repeated) clinical applications, we evaluated its safety, biodistribution and dosimetry.
Four healthy subjects (two females, two males) underwent one whole-body PET/MR measurement lasting for more than 120 min. The GluN2B-specific radioligand (R)-[11C]Me-NB1 was administered simultaneously with the PET start. Subjects were measured in nine passes and six bed positions from head to mid-thigh. Regions of interest was anatomically defined for the brain, thyroid, lungs, heart wall, spleen, stomach contents, pancreas, liver, kidneys, bone marrow and urinary bladder contents, using both PET and MR images. Time-integrated activity coefficients were estimated to calculate organ equivalent dose coefficients and the effective dose coefficient. Additionally, standardized uptake values (SUV) were computed to visualize the biodistribution.
Administration of the radioligand was safe without adverse events. The organs with the highest uptake were the urinary bladder, spleen and pancreas. Organ equivalent dose coefficients were higher in female in almost all organs, except for the urinary bladder of male. The effective dose coefficient was 6.0 µSv/MBq.
The GluN2B-specific radioligand (R)-[11C]Me-NB1 was well-tolerated without reported side effects. Effective dose was estimated to 1.8 mSv when using 300 MBq of presented radioligand. The critical organ was the urinary bladder. Due to the low effective dose coefficient of this radioligand, longitudinal studies for drug development and treatment monitoring of neuropsychiatric disorders including neurodegenerative diseases are possible.
Trial registration Registered on 11th of June 2019 at https://www.basg.gv.at (EudraCT: 2018-002933-39).
The N-Methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion channel involved in physiological processes in synaptic transmission [1]. NMDARs form heterotetrameric complexes comprising mostly two GluN1 and two GluN2 (2A–2D) subunits [2]. Moreover, NMDARs can be divided in synaptic and extrasynaptic receptors. While synaptic NMDAR are linked to protective processes, activated extrasynaptic NMDAR, typically enriched with the GluN2B-subunit, might trigger excitotoxic mechanisms. These are thought to be related to neuropsychiatric disorders such as Alzheimer's disease or depression [3]. Hence, the GluN2B-subunit might be a promising target for drug development and to identify alterations in neuropsychiatric disorders. Unfortunately, GluN2B-specific antagonists such as EVT-101 or CERC-301 only showed results in vitro and had limited effects in clinical studies [4]. The promising GluN2B-selective antagonist CP-101,606 demonstrated similar effects to the anesthetic and rapid-acting antidepressant ketamine but subjects suffered from adverse side effects leading to discontinuation of the study [5]. The possibility to map GluN2B-subunits with and without such antagonists would pave the way to develop novel drugs with a higher efficacy by elucidating their mechanisms of action.
Positron emission tomography (PET) is an important tool in clinical routine to identify tumors or aid the diagnostic process of neuropsychiatric disorders. Moreover, PET is crucial for researching and mapping receptors or to improve drug development by highlighting their modes of action. Recently, the novel GluN2B-subunit NMDAR-specific radioligand (R)-[11C]Me-NB1 was developed in rodents [6] and successfully translated to humans [7] with a high specificity, good test--retest reliability and favorable kinetics. However, it is not only important that the tracer can penetrate the blood–brain barrier and shows promising clinical characteristics, it further has to be safe for human applications in terms of tolerability, with reasonable biodistribution and limited radiation burden. This would enable longitudinal studies with the opportunity to assess interventional effects. Therefore, we investigated the biodistribution, the equivalent organ absorbed dose coefficient and effective dose coefficient of the promising GluN2B-subunit NMDAR-specific radioligand (R)-[11C]Me-NB1.
Four healthy subjects (see Table 1) were recruited for the study. All participants were free from internal, neurological or psychiatric disorders assessed via a thorough medical history, physical examination, electrocardiogram and routine laboratory parameters. Exclusion criteria included neurological diseases or psychiatric disorders, illness 2 weeks prior to recruitment, history of drug or atopic allergy, myocardial infarction, history of cancer, liver or renal disease, family history of prolonged QT-interval, MR or PET contraindications, consumption of tobacco products 3 months before recruitment, history of drug or alcohol abuse, significant prior radiation exposure in the past 10 years and for females breast feeding or pregnancy. Female subjects underwent a urinary pregnancy test at the screening visit and on the measurement day. For safety reasons, vital signs of subjects were measured before and after the PET examination. Participants were observed for 3 h after the end of the scanning procedure to monitor potential adverse events.
Table 1 Subject information
All subjects gave written informed consent after explanation of the study protocol. The study was approved by the Ethics Committee of the Medical University of Vienna (ethics number: 1980/2018) and registered on https://www.basg.gv.at (EudraCT: 2018-002933-39). Procedures were carried out in accordance with the Declaration of Helsinki. Subjects were insured and reimbursed for participation.
Radiosynthesis
Syntheses were performed as previously described [6, 7]. In short, (R)-[11C]Me-NB1 was produced on a fully-automated GE Tracerlab™ FX2 C synthesis module by a methylation reaction. [11C]CH3I was reacted with the enantiomerically pure des-methyl GMP-grade precursor (R)-NB1 in DMF and in the presence of Cs2CO3 and separated from radiochemical impurities via semi-prep HPLC. The final product was purified using solid phase extraction, eluted with 1.5 mL ethanol and formulated for human application using 10 mL of NaCl (0.9%) and 6 mL of phosphate-buffered saline.
Molar activity was 679 ± 207 GBq/µmol at end of syntheses and 328 ± 112 GBq/µmol at the time of application with the limit of molar activity above > 25 GBq/µmol. The limits of (R)-Me-NB1 and precursor NB-1 concentration were both set below < 0.01 mg/mL. Mean injected dose of the active pharmaceutical ingredient (API) (R)-Me-NB1 was 1.6 ± 0.7 ng/kg body weight (female 2.1 ng/kg, male 1.2 ng/kg), while the mean injected dose of tracer was 305 ± 28 MBq. Therefore, the applied concentration was far below the application limits and subsequently, no pharmacokinetic effects are expected or were observed.
All participants underwent one whole-body PET measurement from head to mid-thighs on a fully-integrated PET/MR scanner (Siemens mMR Biograph, Erlangen, Germany). PET data were acquired in nine passes of increasing duration (0.5, 0.5, 0.5, 1, 1, 2, 3, 4 and 7 min per bed position) in six bed positions, yielding a measurement time of more than 2 h. The radioligand (R)-[11C]Me-NB1 was administered as short bolus via a cubital vein (mean injected dose: 305 ± 28 MBq; 4.4 ± 1.1 MBq/kg body weight). Subsequently, the cannula was flushed with saline. Subjects were instructed not to fall asleep and to let their thoughts wander.
During all nine passes, a two-point DIXON sequence (DIXON, TE/TR = 2.46/3.6 ms, flip angle = 10°, voxel size = 2.6 × 2.6 × 3.1 mm3) was conducted during breath hold after exhalation in each bed position yielding nine whole body DIXON attenuation correction (AC) maps [8]. Due to the short frame durations, no breathing commands were given during the first five cycles. The AC maps were segmented into bone, lung, soft and fatty tissue and air.
Additionally, in the ninth cycle, a T2-weighted MR image was acquired (TE/TR = 121/1400 ms, flip angle = 133°, voxel size = 1.5 × 1.5 × 7.2 mm3) in each bed position to rule out gross anatomical abnormalities.
PET processing
The 3D list-mode PET data were reconstructed with an ordinary Poisson-ordered subset expectation maximization algorithm (OP-OSEM, 3 iterations, 21 subsets). Data were corrected for attenuation, scatter, randoms and dead time. AC of the first five passes was performed with the DIXON AC map of the sixth pass due to omitted breathing commands for the first passes. Passes six to nine were corrected with the corresponding AC map. Decay correction was performed for calculation of standardized uptake values (SUV) only. SUV was defined as
$${\text{SUV}} = \frac{{\text{activity concentration}}}{{\left( {{\text{injected dose}}/{\text{body weight}}} \right)}}$$
Biodistribution and dosimetry
Regions of interest (ROIs) were manually drawn on the PET images for brain, thyroid, lungs, heart wall, liver, spleen, kidneys, stomach (fundus), pancreas, bone marrow (substituted by the vertebrae L4 and L5 [9]) and urinary bladder contents using PMOD 4.2 (PMOD Technologies LLC, Zurich, Switzerland). The bladder was delineated with respect to the volume change over the measurement time. PET visualization thresholds were set individually for each subject. The threshold was set as low as possible to visualize the organs, while ROIs were drawn to cover most of the organs, but also to leave enough space to the borders and other organs to omit partial volume and breathing artifacts. The localization of each ROI was crosschecked with the matching MR image.
To estimate the effective dose coefficient, time activity curves (TACs) were extracted for all mentioned ROIs using PMOD. The cumulative activity (kBq × h) was defined as the non-decay corrected area under the curve (AUC; kBq/mL × h), utilizing a trapezoid method, multiplied by the respective mass of the organ (mo; male or female) of the OLINDA/EXM International Commission on Radiation Protection 89 (ICRP89) phantom. As the previous integration using the trapezoid function covers more than five physical half-lives of the carbon-11, the AUC from the last time point to infinity (AUCinf) was mathematically added, assuming only physical decay, as follows:
$${\text{AUC}}_{{{\text{inf}}}} = \frac{{A_{{{\text{last}}}} }}{k}$$
where Alast is the activity measured in the last time point and k represents decay constant of carbon-11. Subsequently, the cumulative activity was normalized by the injected dose (ID; kBq) yielding time-integrated activity coefficients (TIAC; h). Finally, the resulting TIACs were multiplied by the factor between the subject's weight (ms; kg) and the phantom weight (mp; 60 kg and 73 kg for females and males, respectively) and were averaged for the male and female models. The TIAC for one organ of an individual subject was calculated as follows:
$${\text{TIAC}} = \frac{{AUC \times m_{o} }}{ID} \times \frac{{m_{s} }}{{m_{p} }}$$
The TIACs of all mentioned ROIs were entered into OLINDA/EXM 2.1 (Hermes Medical Solution, Stockholm, Sweden) [10] for each sex to obtain organ equivalent dose coefficients (h; Sv/Bq) and contributions to effective dose coefficients (econ; Sv/Bq) with tissue weighting factors (wr) according to ICRP 103 [11]. The relationship between econ and h for each organ can be then defined as:
$$e_{{{\text{con}}}} \left( o \right) = w_{r} \left( o \right) \times h\left( o \right)$$
The TIAC of the total remainder of the body was estimated as the theoretical TIAC for carbon-11 (T1/2/ln(2) = 0.49 h, with T1/2 being the physical half-life of the radionuclide [12]) minus the sum of the regional TIACs.
$${\text{TIAC}}_{{{\text{remainder}}}} = \frac{{T_{1/2} }}{{{\text{ln}}\left( 2 \right)}} - \mathop \sum \limits_{o} {\text{TIAC}}\left( o \right)$$
No gastrointestinal transit or bladder voiding model was used for a conservative estimation of the effective dose (E; Sv). In a final step, the effective dose coefficient (e; Sv/Bq) was calculated as the averaged sum over the organs
$$e = \mathop \sum \limits_{o} \frac{{e_{{{\text{con}}}} \left( o \right)^{{{\text{male}}}} + e_{{{\text{con}}}} \left( o \right)^{{{\text{female}}}} }}{2}$$
The GluN2B-specific radioligand (R)-[11C]Me-NB1 was well-tolerated by all subjects, and no side effects or adverse events were reported during the measurement or the subsequent 3-h time interval. The limit for the API in the clinical PET studies were set at a level of 10 µg/mL (overall max. 0.175 mg/production batch). Based on animal toxicity studies, the administered mean injected dose (1.6 ± 0.7 ng/kg body weight) was 62,500-fold lower than the no-observed-adverse-effect level (NOAEL) for (R)-Me-NB1. Vital signs were comparable prior and after the measurement. Furthermore, all subjects successfully passed the final screening visit.
Biodistribution
(R)-[11C]Me-NB1 biodistribution is shown in Fig. 1. A video of the activity change per pass can be found in Online Resource 1 (not decay corrected) (Additional file 1). Initial high activity was found in the thyroid, lungs, spleen, kidneys and pancreas. While most of the mentioned regions showed a quick activity washout, the pancreas indicated clearance at a later time point of the measurement. The volume and activity concentration change in the urinary bladder is clearly visible over the measurement period. Importantly, the radioligand passed the blood–brain barrier within the first minutes. SUV TACs of all subjects are shown in Fig. 2. The radioligand was quickly washed out from the heart wall, lungs, spleen and the kidneys. Slower kinetics were observed in the liver and the brain. Interestingly, the bone marrow almost reached a steady state over the course of the 2-h measurement. The highest SUV by far was found in the urinary bladder, followed by the pancreas and spleen. There was no visual SUV difference between male and female subjects.
Tracer distribution over time of one representative subject. Depicted is an MR image for anatomical comparison to the PET images: a activity in kBq/cc (not decay corrected); b standardized uptake value (SUV; decay corrected). The radioligand (R)-[11C]Me-NB1 showed high initial uptake in the thyroid, lungs, spleen, pancreas and kidneys. In contrast, activity in the bone marrow (substituted by the vertebrae L4 and L5) and the liver built up over a longer period. Increase in the bladder volume over time is clearly visible. The first seven cycles are shown because of the advanced time and the low activity in the last cycles
Standardized uptake values of all subjects across time (decay corrected). In the heart wall, kidneys and lungs a fast washout can be observed. Brain, liver and especially bone marrow show slower kinetics
The TIACs of all delineated ROIs are given in Table 2. The highest TIAC was found in the urinary bladder content of one male subject with an at least 4 times higher value than in the same region of the other subjects. Other ROIs with high TIACs included the liver, brain and bone marrow. In Table 3, the equivalent dose coefficient and effective dose coefficient calculated with OLINDA/EXM are shown. Since the tissue radiation weighting factor wr for electrons and photons for gamma and beta radiation is equal to 1, equivalent dose coefficients calculated with OLINDA/EXM are the same as individual organ an absorbed dose coefficients. Contribution to effective dose coefficient was the highest in the urinary bladder wall (1.5 µSv/MBq, one male subject with at least threefold higher dose compared to the other subjects) followed by the stomach wall (1.0 µSv/MBq) and the lungs (0.7 µSv/MBq). The regions with the lowest doses for all subjects included the salivary glands, thymus and small intestine. The effective dose coefficient was estimated at 6.0 µSv/MBq.
Table 2 Time-integrated activity coefficients in hours (h)
Table 3 Organ equivalent doses and contribution to effective doses coefficient
In this study, we evaluated the safety, biodistribution and dosimetry of the promising GluN2B-specific NMDAR radioligand (R)-[11C]Me-NB1 in humans. The radioligand was well-tolerated by all subjects and no adverse events were reported. The effective dose coefficient was 6.0 µSv/MBq with the urinary bladder as the critical organ (contribution to effective dose coefficient: 1.5 µSv/MBq). Of note, the no bladder voiding model was applied for conservative estimation of effective dose coefficient, as PET measurement durations of 120 min (i.e., approx. six half-lives) are common.
The calculated effective dose coefficient of 6.0 µSv/MBq is similar to other carbon-11 tracers such as [11C]Raclopride [13], [11C]FLB 457 [14] or [11C]PE2I [15]. In comparison with other PET radioisotopes, it is lower than [64Cu]DOTA-AE105 (31.5 µSv/MBq) [16] or [18F]FDG (19.0 µSv/MBq) [17]. On the other hand, the effective dose coefficient of (R)-[11C]Me-NB1 is higher than that of [15O]water (0.9 µSv/MBq) [18]. Usually, sex differences are observed with a higher equivalent dose coefficient in females than in males. This might be caused by a smaller model in the OLINDA/EXM software where organs are closer together and therefore, irradiating each other to a higher degree than in the male model [12]. Another cause could be the additional radiation exposure of breasts and uterus [19]. Also in this study sex differences were found in most of the regions but not in the equivalent dose coefficient. A reason might be the high urinary bladder uptake of the first male subject. Whether this value was an outlier or valid remains unknown because of the small sample size.
Interestingly, Zanotti-Fregonara et al. recently discussed the necessity of carbon-11 dosimetry studies in general [20]. The effective dose coefficient relies on the applied methodology, including if a bladder voiding model was used. Comparing the effective dose coefficient of the same carbon-11 tracers in two or more studies, performed by different groups, revealed an average difference of more than 40% in the majority of the studies. However, the variability in the effective dose coefficient across all investigated carbon-11 dosimetry studies was small. In consequence, the authors stated dosimetry studies with such short-lived radionuclides may be unnecessary in the future, both in animals and humans and radiation exposure could be avoided. Instead, it was proposed that a value of 5.0 µSv/MBq should be applied to studies using carbon-11 tracers, which was the average across all investigated studies [20]. We support this notion to protect animals and humans from potentially harmful and unnecessary irradiation. In addition, avoiding dosimetry studies of carbon-11 tracers, would decrease the financial burden and avoid the use of the resources of the institution.
Applying the effective dose coefficient found in this study (i.e., 6.0 µSv/MBq) would yield a dose of 2.7 mSv for a 75 kg person and an administered dose of 6.0 MBq/kg [7]. According to the Austrian Medical Radiation Protection law, subjects are allowed to receive a dose of 30.0 mSv within 10 years, excluding medically indicated examinations or studies with a benefit for the individual. In addition, organ absorbed doses presented in this study are all below the threshold doses for the occurrence of deterministic radiation effects. In the European Union, individual regulations apply. Under the regulations of the Radioactive Drug Research Committee (RDRC) applied in the USA, doses are limited up to 50.0 mSv per single dose and 150.0 mSv per year, depending on the organ. Differently, the ICRP recommends a yearly effective dose of < 10.0 mSv. In any of the mentioned regulations, longitudinal studies with (R)-[11C]Me-NB1 are feasible with several measurements per year, enabling drug development and interventional studies. Moreover, during PET/CT measurements, CT contributes with a significant portion of the radiation dose hence using MR imaging instead of classical CT helps to keep the radiation dose as reasonably low as possible. Alternatively, one could consider use of the low-dose CT to prevent an extra radiation burden to measured subject or personnel.
Although the effective dose coefficient of 6.0 µSv/MBq was similar to other studies, we have to mention a few limitations. The sample size was relatively small and only young adults were recruited. Another issue might be the use of a PET/MR with MR-based AC. While the MR has the advantage of no additional irradiation and a higher contrast for soft tissue, the MR-based AC method DIXON is known to underestimate activity. However, we used a method extending the AC map with bone models to mitigate this effect [8]. Finally, the ninth pass lasted more than 7 min in each bed position (total pass > 42 min). Yet, the second to sixth bed positions were decay corrected to the first, assuming only physical decay. Nonetheless, at the ninth pass, approximately more than five half-lives had already passed and little activity was left (see seventh cycle of Fig. 1).
The Glu2NB-subunit NMDAR-specific radioligand (R)-[11C]Me-NB1 is safe to be applied in clinical studies. The dosimetry study revealed an effective dose coefficient of 6.0 µSv/MBq with the critical organ being the urinary bladder. Considering a reasonable dose of 500 MBq, this would yield an effective dose of 3.0 mSv. Thus, the radioligand enables longitudinal studies investigating the GluN2B-subunit NMDAR for drug development, interventional studies and alterations in neuropsychiatric disorders including neurodegenerative diseases under the commonly applied regulations of the RDRC and the ICRP guidelines.
Raw data are not available due to reasons of data protection. Processed data are available from the corresponding author on reasonable request and a data-sharing agreement.
Attenuation correction
AUC:
Area under the curve
ICRP89:
International commission on radiation protection 89
NMDAR:
NMDA receptor
NOAEL:
No-observed- adverse-effect level
OP-OSEM:
Ordinary Poisson-ordered subset expectation maximization algorithm
RDRC:
Radioactive drug research committee
Standardized uptake values
TAC:
Time activity curves
TIAC:
Time-integrated activity coefficient
Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev. 1999;51:7–61.
Paoletti P, Bellone C, Zhou Q. NMDA receptor subunit diversity: Impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci. 2013;14:383–400.
Hardingham GE, Bading H. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci. 2010;11:682–96.
Ibrahim L, Diazgranados N, Jolkovsky L, Brutsche N, Luckenbaugh DA, Joseph Herring W, et al. A randomized, placebo-controlled, crossover pilot trial of the oral selective NR2B antagonist MK-0657 in patients with treatment-resistant major depressive disorder. J Clin Psychopharmacol. 2012;32(4):551–7.
Machado-Vieira R, Henter ID, Zarate CA. New targets for rapid antidepressant action. Progress Neurobiol. 2017;152:21–37.
Haider A, Herde AM, Krämer SD, Varisco J, Keller C, Frauenknecht K, et al. Preclinical evaluation of benzazepine-based PET radioligands (R)- And (S)-11C-Me-NB1 reveals distinct enantiomeric binding patterns and a tightrope walk between GluN2B- And S1-receptor–targeted PET imaging. J Nucl Med. 2019;60(8):1167–73.
Rischka L, Vraka C, Pichler V, Rasul S, Nics L, Gryglewski G, et al. First-in-human brain PET imaging of the GluN2B-containing N-methyl-D-aspartate receptor with (R)-11 C-Me-NB1. J Nucl Med. 2021. https://doi.org/10.2967/jnumed.121.262427.
Paulus DH, Quick HH, Geppert C, Fenchel M, Zhan Y, Hermosillo G, et al. Whole-body PET/MR imaging: quantitative evaluation of a novel model-based MR attenuation correction method including bone. J Nucl Med. 2015;56(7):1061–6.
Johansen A, Holm S, Dall B, Keller S, Kristensen JL, Knudsen GM, et al. Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions. EJNMMI Res. 2019;9(1):71.
Stabin MG, Siegel JA. RADAR dose estimate report: A Compendium of radiopharmaceutical dose estimates based on OLINDA/EXM version 2.0. J Nucl Med. 2018;59(1):154–60.
ICRP. Annals of the ICRP Published on behalf of the International Commission on Radiological Protection International Commission on Radiological Protection Main Commission of the ICRP Corresponding members. Ann ICRP. 2007;103.
Bullich S, Slifstein M, Passchier J, Murthy NV, Kegeles LS, Kim JH, et al. Biodistribution and radiation dosimetry of the glycine transporter-1 ligand 11C-GSK931145 determined from primate and human whole-body PET. Mol Imaging Biol. 2011;13(4):776–84.
Slifstein M, Hwang DR, Martinez D, Ekelund J, Huang Y, Hackett E, et al. Biodistribution and radiation dosimetry of the dopamine D2 ligand 11C-raclopride determined from human whole-body PET. J Nucl Med. 2006;47(2):313–9.
Kimura Y, Ito H, Shiraishi T, Fujiwara H, Kodaka F, Takano H, et al. Biodistribution and radiation dosimetry in humans of [11C]FLB 457, a positron emission tomography ligand for the extrastriatal dopamine D2 receptor. Nucl Med Biol. 2014;41(1):102–5.
Ribeiro MJ, Ricard M, Lièvre MA, Bourgeois S, Emond P, Gervais P, et al. Whole-body distribution and radiation dosimetry of the dopamine transporter radioligand [11C]PE2I in healthy volunteers. Nucl Med Biol. 2007;34(4):465–70.
Persson M, El Ali HH, Binderup T, Pfeifer A, Madsen J, Rasmussen P, et al. Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging. Nucl Med Biol. 2014;41(3):290–5.
Brix G, Lechel U, Glatting G, Ziegler SI, M̈nzing W, Müller SP, et al. Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations. J Nucl Med. 2005;46(4):608–13.
Towson JEC. Radiation Dosimetry and Protection in PET. In: Positron Emission Tomography. Springer, London; 2006. p. 251–65. Available from: https://link.springer.com/chapter/https://doi.org/10.1007/1-84628-007-9_12
Hatano M, Miyazaki T, Ishiwata Y, Nakajima W, Arisawa T, Kuroki Y, et al. Biodistribution and radiation dosimetry of the positron emission tomography probe for AMPA receptor, [11C]K-2, in healthy human subjects. Sci Rep. 2021;11(1):1598.
Zanotti-Fregonara P, Lammertsma AA, Innis RB. 11C dosimetry scans should be abandoned. J Nucl Med. 2021;62:158–9.
The authors are particularly grateful to Pia Baldinger-Melich and Paul Michenthaler for clinical support. We thank Vera Ritter, Christoph Wotawa, Daniel Pacher, Sebastian Klug, Harald Ibeschitz, Natalie Schindler, Karsten Bamminger, Tim Wollenweber and Marius Ozenil for technical support. Furthermore, the authors also thank Yves Auberson and Nicholas Seneca from Novartis for their technical support.
This project was supported in part by the Swiss National Science Foundation grant numbers 310030E-160403/1 and 310030E-182872/1 to Prof. Simon M. Ametamey. Matej Murgaš is funded by the Austrian Science Fund FWF DOC 33-B27. Murray B. Reed and Leo R. Silberbauer are recipients of a DOC fellowship of the Austrian Academy of Sciences.
Lucas Rischka and Matej Murgaš have contributed equally.
Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
Lucas Rischka, Matej Murgaš, Dietmar Winkler, Leo Robert Silberbauer, Murray Bruce Reed, Godber Mathis Godbersen, Jakob Unterholzner, Patricia Handschuh, Gregor Gryglewski, Andreas Hahn & Rupert Lanzenberger
Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
Verena Pichler, Chrysoula Vraka, Lukas Nics, Sazan Rasul, Thomas Mindt, Markus Mitterhauser, Wolfgang Wadsak & Marcus Hacker
Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria
Verena Pichler
Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
Ivo Rausch
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland
Simon Mensah Ametamey
Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria
Thomas Mindt & Markus Mitterhauser
Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
Thomas Mindt
Center for Biomarker Research in Medicine (CBmed), Graz, Austria
Wolfgang Wadsak
Lucas Rischka
Matej Murgaš
Chrysoula Vraka
Dietmar Winkler
Lukas Nics
Sazan Rasul
Leo Robert Silberbauer
Murray Bruce Reed
Godber Mathis Godbersen
Jakob Unterholzner
Patricia Handschuh
Gregor Gryglewski
Markus Mitterhauser
Andreas Hahn
Rupert Lanzenberger
Marcus Hacker
SMA, TM, DW, WW, MM, RL and MH had the idea for the project. RL, GG, PH, VP and SMA designed the study and wrote the protocol. Data were acquired by LR, VP, CV, IR, LN, SR, MMu, MR, GG, LS, JU and CW. LR analyzed the data. LR, AH and RL prepared the manuscript. All authors reviewed and agreed on the final version of the manuscript.
Correspondence to Rupert Lanzenberger or Marcus Hacker.
The study was approved by the Ethics Committee (ethics number: 1980/2018) of the Medical University of Vienna. Procedures were carried out in accordance with the Declaration of Helsinki.
All subjects gave written informed consent after detailed explanation of the study procedure.
S. M. Ametamey is co-inventor of the filed patent number US2017/0224852A1. R. Lanzenberger received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. D. Winkler received lecture fees/authorship honoraria within the last three years from Angelini, Lundbeck, MedMedia Verlag, and Medical Dialogue. Without relevance to this work, W. Wadsak received within the last 3 years research grants from ITM Medical Isotopes GmbH (Munich, Germany) and Scintomics (Fürstenfeldbruck, Germany). Without relevance to this work, M. Mitterhauser is scientific advisor for ROTOP Pharma GmbH. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Additional file 1. A video showing the time change of activity distribution in whole body (not decay corrected).
Rischka, L., Murgaš, M., Pichler, V. et al. Biodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[11C]Me-NB1. EJNMMI Res 12, 53 (2022). https://doi.org/10.1186/s13550-022-00925-8
GluN2B-subunit
Neuropsychiatric disorders


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redpajama_set_name: RedPajamaCommonCrawl


text:
use math::sqrtf;
use utils::Point3;
use motor::Motor;
use hardware::peripherals::time::Time;

pub trait MotionPlanner {
    fn set_target(&mut self, target: Point3);
    fn update(&mut self);
}

pub struct CartesianMotionPlanner<'a> {
    x_motor: &'a mut Motor,
    y_motor: &'a mut Motor,
    z_motor: &'a mut Motor,
    time: &'a Time,
    max_acceleration: f32,
    max_speed: f32,
    start_speed: f32,
    end_speed: f32,
    motion_distance: f32,
    delta_x: f32,
    delta_y: f32,
    delta_z: f32,
    top_x_speed: f32,
    top_y_speed: f32,
    top_z_speed: f32,
    start_time: u32,
    transition1: u32,
    transition2: u32,
    end_time: u32,
    set_start: bool,
}

impl<'a> CartesianMotionPlanner<'a> {
    pub fn new(
        x_motor: &'a mut Motor,
        y_motor: &'a mut Motor,
        z_motor: &'a mut Motor,
        time: &'a Time,
        max_acceleration: f32,
        max_speed: f32,
        start_speed: f32,
        end_speed: f32,
    ) -> CartesianMotionPlanner<'a> {
        CartesianMotionPlanner {
            x_motor: x_motor,
            y_motor: y_motor,
            z_motor: z_motor,
            time: time,
            max_acceleration: max_acceleration,
            max_speed: max_speed,
            start_speed: start_speed,
            end_speed: end_speed,
            motion_distance: 0.0,
            delta_x: 0.0,
            delta_y: 0.0,
            delta_z: 0.0,
            top_x_speed: 0.0,
            top_y_speed: 0.0,
            top_z_speed: 0.0,
            start_time: 0,
            transition1: 0,
            transition2: 0,
            end_time: 0,
            set_start: false,
        }
    }

    fn get_axis_top_speed(&self, delta: f32, top_speed: f32) -> f32 {
        let speedup_distance = top_speed / self.max_acceleration;
        if speedup_distance < delta / 2.0 {
            (delta / 2.0) * self.max_acceleration
        } else {
            top_speed
        }
    }

    #[inline]
    fn translate_to_axis(&self, delta: f32, axis_speed: f32) -> f32 {
        (axis_speed * delta) / self.motion_distance
    }

    fn get_current_position(&self) -> Point3 {
        Point3::new(
            self.x_motor.get_position(),
            self.y_motor.get_position(),
            self.z_motor.get_position(),
        )
    }

    fn get_current_velocity(&self) -> Point3 {
        Point3::new(
            self.x_motor.get_velocity(),
            self.y_motor.get_velocity(),
            self.z_motor.get_velocity(),
        )
    }
}

impl<'a> MotionPlanner for CartesianMotionPlanner<'a> {
    fn set_target(&mut self, point: Point3) {
        let current_position = self.get_current_position();
        self.delta_x = point.x - current_position.x;
        self.delta_y = point.y - current_position.y;
        self.delta_z = point.z - current_position.z;
        self.motion_distance = sqrtf(
            self.delta_x * self.delta_x + self.delta_y * self.delta_y + self.delta_z * self.delta_z,
        );
        self.top_x_speed = self.translate_to_axis(
            self.delta_x,
            self.get_axis_top_speed(self.delta_x, self.max_speed),
        );
        self.top_y_speed = self.translate_to_axis(
            self.delta_y,
            self.get_axis_top_speed(self.delta_y, self.max_speed),
        );
        self.top_z_speed = self.translate_to_axis(
            self.delta_z,
            self.get_axis_top_speed(self.delta_z, self.max_speed),
        );
        self.transition1 = ((self.max_speed - self.start_speed) / self.max_acceleration) as u32;
        let part1_distance = self.start_speed * self.transition1 as f32 +
            (1.0 / 2.0) * self.max_acceleration * (self.transition1 * self.transition1) as f32;
        let part3_time = ((self.max_speed - self.end_speed) / self.max_acceleration) as u32;
        let part3_distance = self.start_speed * part3_time as f32 +
            (1.0 / 2.0) * self.max_acceleration * (part3_time * part3_time) as f32;
        self.transition2 =
            (self.motion_distance - (part1_distance + part3_distance) / self.max_speed) as u32;
        self.end_time = self.transition2 + part3_time;
        self.set_start = true;
    }

    fn update(&mut self) {
        if self.set_start {
            self.start_time = self.time.now();
            self.set_start = false;
        }
        let now = self.time.now() - self.start_time;
        // TODO account for now is negative?
        let current_speed;
        if now < self.transition1 {
            current_speed = now as f32 * self.max_acceleration + self.start_speed as f32;
        } else if now >= self.transition1 && now < self.transition2 {
            current_speed = self.max_speed;
        } else if now >= self.transition2 && now < self.end_time {
            current_speed = now as f32 * self.max_acceleration * -1.0 + self.max_speed;
        } else {
            current_speed = self.end_speed;
        }
        // TODO Handle set_current_velocity failure.
        self.x_motor
            .set_velocity((current_speed * self.delta_x) / self.motion_distance);
        self.y_motor
            .set_velocity((current_speed * self.delta_y) / self.motion_distance);
        self.z_motor
            .set_velocity((current_speed * self.delta_z) / self.motion_distance);
    }
}

redpajama_set_name: RedPajamaGithub


text:
Ernst Leo "Golli" Marboe (* 4. August 1965 in Wien) ist ein österreichischer Medienexperte, Journalist, Buchautor, Vortragender an Hochschulen und Speaker zu Medienfragen und Obmann des Vereins zur Förderung eines selbstbestimmten Umgangs mit Medien. Davor war er 25 Jahre auch als TV- und Filmproduzent tätig.

Leben
Golli Marboe wurde als Sohn des ORF-Intendanten Ernst Wolfram Marboe und dessen Frau Maria geboren. Sein Großvater ist der Schriftsteller und prägende Leiter der Bundestheaterverwaltung Ernst Marboe, sein Onkel der Jurist und Wiener Kultur-Stadtrat (1996–2001) Peter Marboe. Er ist verheiratet und hat vier Kinder. Prägend war für Golli Marboe die Schulzeit im katholischen Schottengymnasium.

Nach seiner Matura 1984 studierte er Theaterwissenschaft und Politikwissenschaften an der Universität Wien.

Von 1984 bis 1992 wirkte Golli Marboe als Regieassistent und Aufnahmeleiter bei ungefähr 25 Filmen bzw. Serien, unter anderem bei Produktionen von Michael Kehlmann, Peter Weck oder Fritz Eckhardt, und bei internationalen Filmen, wie "Der Fall Franza" (Xaver Schwarzenberger, Armin Müller Stahl), "From Time to Time" (Michel Piccoli, Jeremy Irons), "Shining Through" (Michael Douglas, Melanie Griffith), "The Train" (Ben Kingsley), "The Living Daylights" (James Bond)...

1992 gründete er die Produktionsfirma "Sternstunden", die hunderte TV-Sendungen produzierte und 1999 Insolvenz anmelden musste. Die erste österreichische Privat-TV-Minute von W1 wurde aus dem Sternstunden-Studio ausgestrahlt. Die von Sternstunden entwickelte Comedy-Serie "Die kranken Schwestern" (uA mit Florian Scheuba, Viktor Gernot, Werner Sobotka, Uli Bree, Rupert Henning) wurde als innovativstes Projekt des Jahres 1997 mit der Romy ausgezeichnet.

1999 bis 2011 war Marboe Producer bei der Münchner Firma Tellux, in der er ca. 200 Filme und ebenso viele Magazin-Sendungen schuf. Unter anderem zeichnete er für die Entwicklung und Produktion der mit dem Grimme-Preis 2011 ausgezeichnete Kinderserie "Schnitzeljagd im Heiligen Land" verantwortlich.

Seit 2003 ist er Dozent an der Donauuniversität in Krems.

2007/2008 bis 2011 war er Geschäftsführer bei Tellux-Film Stuttgart, IFAGE Wiesbaden und Merkur TV.

2011 gründete er die makido film, die jedoch 2015 Insolvenz anmelden musste. Sie produzierte u. a. für die ORF-Formate Universum, Newton, Orientierung und auch für das ZDF, Arte, 3sat, RAI, diverse ARD-Anstalten (BR, WDR, HR, MDR, RBB,..), SRF,  oder  KIKA.

Seit 2015 ist er als freier Journalist und Konsulent u. a. für Die Furche oder den ORF tätig.

2016 gründete Golli Marboe den Verein Verein zur Förderung eines selbstbestimmten Umgangs mit Medien (VsUM) und fungiert als Obmann. VsUM hat sich zum Ziel gesetzt, das Medienbewusstsein unserer Gesellschaft im Sinne demokratischer Grundwerte zu stärken. Dazu veranstaltet der Verein Symposien, diverse Vorträge oder initiiert Lehrfilme, die dann von Bildungseinrichtungen, wie dem BMB, dem Österreichischen Bildungsministerium oder mit Matthias Film in Deutschland vertrieben und von der Wiener Produktionsfirma Inspiris Film hergestellt werden.

Darüber hinaus unterrichtet er an Bildungseinrichtungen, wie der Universität Wien im Fachbereich Publizistik, der Fachhochschule der WKW, der KMA (Katholischen Medienakademie) "Journalismus im Bewegtbild", "Medieninnovation", "Storytelling" und mehr. Er wirkt als Vortragender für Schulleiterinnen und Schulleiter an diversen Pädagogische Hochschulen, wie der KPH oder der PH NÖ. Dort spricht er über Medienerziehung und den Themenschwerpunkt: "Medien-Bildung-Demokratie".

Als Speaker fungierte Marboe unter anderem für die WU Wien oder bei der Westbalkan Medienkonferenz der EU als Medienexperte mit dem Schwerpunkt "Wesen und Zukunft des Öffentlich-Rechtlichen Rundfunks". Anlässlich der Nationalratswahl in Österreich 2017 gründete Golli Marboe die Initiative zur "Dirndlkoalition" – mit dem Ziel, eine Beteiligung der FPÖ an einer nächsten Regierung zu verhindern und die Idee einer "schwarz-grün-pinken" Koalition zu unterstützen. Seit Sommer 2018 ist Golli Marboe Mitglied der Kardinal-König-Stiftung, seit 2021 Vorsitzender des Bereichs "Medien" der Kosovo-Friends.

Mitgliedschaften
 Akademie des Österreichischen Films
 Deutsche Akademie für Fernsehen
 Gesellschaft katholischer Publizisten Deutschlands
 Initiative Weltethos
 Kardinal-König-Stiftung
 Kosovo-Friends, Vorsitzender Bereich "Medien"
 Medien-Bildung-Demokratie e.V., Gründungsmitglied
 ORF-Publikumsrat seit 2018
 Presseclub Concordia
 Verband katholischer Publizistinnen und Publizisten Österreichs
 Vereinigung für Medienkultur
 Verein zur Förderung eines selbstbestimmten Umgangs mit Medien, Obmann

Filmografie (Auswahl)
 2015 Abenteuer Alpen, Dreiteiler mit Reinhold Messner, ARD, ORF
 2015 Strafsache Luther – Wie Rom die Reformation verhindern wollte, MDR, ARTE, ORF, Matthias-Film, Planet TV, Bibel TV, Fernsehfonds Austria
 2015 Topf und Söhne, MDR
 2015 Burgenlandroma auf Wallfahrt – eine Kulturreise, Schau TV, Planet, Kultur Burgenland
 2014 Akte Grüninger, Kinofilm
 2014 Diplomatische Liebschaften – Die Mätressen des Wiener Kongress
 2014 Reporter – Gründüngers Erbe, SRF
 2014 Zwei Päpste für ein Halleluja, Schau TV, Planet
 2014 Jenseits des Jordan, 3sat
 2014 Newton – Jordanien – Wenn die Stadt und ein Meer verschwindet, ORF
 2014 Wir machen Theater solange wir können – 125 Jahre Wiener Volkstheater, 3sat, Volkstheater Wien
 2014 Die Spur der Ahnen – Jede Familie hat ein Geheimnis, MDR
 2014 Die Gerechten unter den Völkern – Retter und Helfer im Nationalsozialismus, Deutsche Welle, Planet TV, ZDF info, 3sat
 2014 Cultus Heilige, Dokureihe 26 × 12/25 Minuten, ORF III, Planet TV, ARD-alpha
 2014 Der Mann, der die Welt reformierte – Lukas Cranach und Martin Luther, MDR
 2013 Geister, die sich scheiden – Richard Strauss und Kurt Weill, 3sat, ORF
 2013 Liedestoll – Angelika Kirschschlager und Konstantin Wecker, Konzert und Dokumentationsaufzeichnung, 3sat, Arthaus
 2013 In bester Verfassung?, MDR
 2013 Mythos Gerechtigkeit, 3sat, BMBF
 2013 Schau in meine Welt – Jonas und die schwarze Meute, MDR
 2013 Wagner vs. Verdi, 6-teilige Dokureihe, ZDF, ARTE; ORF III, Unitel, BMBF
 2013 Der fünfte Akt des Lebens – Revolution der Altersbilder, 3sat, BMBF
 2013 Wahnsinn, Wagner! ZDF, ARTE, Unitel, BMBF
 2013 Leben als Gesamtkunstwerk – Henry van de Velde in Weimar, MDR
 2013 Jesus und die verschwundenen Frauen. ORF, ZDF, SRF, BMUKK
 2013 Georg Kreisler gibt es gar nicht, ZDF, ARTE, ORF III, Filmfonds Wien
 2013 Kreislers musikalische Stolpersteine, ARTE live
 2013 Schau in meine Welt! Khuyagaa – Ein Tag im Leben eines Nomadenjungen, KIKA
 2012 Die Papstmacher, ORF
 2012 Cultus Feiertage, 26-teilige Dokureihe, ORF III, Planet TV; Ordensgemeinschaften Österreich, Kultur Niederösterreich
 2012 Diese verfluchten Stunden am Abend – Häftlingsbordelle im KZ, ORF, ZDF info, MDR, 3sat, Spiegel Geschichte, Nationalfonds, Kulturland Oberösterreich
 2012 Die Ballclique, 20-teilige Dokusoap, KIKA, ORF, ARD, ZDF, Fernsehfonds Austria
 2011 Und die Bibel hat doch recht, ZDF
 2010 Der Kardinal (König), Spieldokumentation von Andreas Gruber, ORF, Autentic, BMUKK
 2008 Augustinus TV-Film 2 Teile, BR
 2008 Tatort: Häschen in der Grube, BR
 2007 Baching, Spielfilm, BR
 2006 Lawine, Spielfilm, BR, ORF

 2011 Campo Santo, Doku (30min), Servus TV
 2011 Imperium Piraten, Doku (45min), ZDF
 2011 Imperium Ritter, Doku (45min), ZDF
 2011 Imperium Wilder Westen, Doku (45min), ZDF
 2011 Dreigroschenoper, Doku (45min), ARTE, ZDF
 2011 Being Liszt, Doku (45min), ARTE, ZDF
 2011 Carmina Burana, Doku (45min), ARTE, ZDF

 2011 Schnitzeljagd im Heiligen Land, Doku (4x30min), Ki.Ka
 2010 Tatort in Fatima, TV-Film (90min), BR
 2010 Pius XII, TV-Film, ARD
 2010 Meine Zeit wird kommen – Gustav Mahler, Doku (52min), ORF, BR, 3sat, SF, BMUKK, Unitel
 2010 Augustinus der Wahrheitssucher, Doku (45min), BR
 2010 Missbraucht und vergessen, Doku (45min), BR, ORF
 2010 Kaprun, Doku (60min), ORF, 3sat
 2010 SOS – Das andere Zuhause, Dokureihe (8x45min), Puls4
 2010 Der Traum vom gelobten Land, Doku (45min), ORF, ZDF
 2010 Die Kirche der Queen, Doku (45min), BR
 2010 Helden des Glaubens, Doku (45min), ORF
 2010 Mächte der Finsternis, Doku (90min), BR, ORF
 2010 Konklave, Doku (45min), ZDF
 2010 Klostergeheimnisse, Dokureihe (10x), Servus TV
 2009 Empathie, TV-Film, BR-alpha
 2009 Der Auftrag des Erzengels, Doku (45min), ZDF
 2009 Credo: Gottes Werk und Darwins Beitrag, Doku (45min), BR, ORF
 2009 Credo: Gott und Weltall, Doku (45min), BR, ORF
 2009 Credo: Väterbilder, Doku (45min), BR, ORF
 2009 Die Macht der Engel, Doku (45min), ZDF
 2009 Alpenklöster Stift Rein, Doku (45min), BR, ORF/3sat
 2009 Alpenklöster Mehrerau, Doku (45min), BR, ORF/3sat
 2009 Alpenklöster Taime, Doku (45min), BR, ORF/3sat
 2009 Alpenklöster Muri Gries, Doku (45min), BR, ORF/3sat
 2009 Alpenklöster Ettal, Doku (45min), BR, ORF/3sat
 2009 Alpenklöster St.Johann Müstair, Doku (45min), BR, ORF/3sat
 2009 Imperium Kalifen, Doku (45min), ZDF
 2009 Imperium Samurai, Doku (45min), ZDF
 2009 Imperium Maharadschas, Doku (45min), ZDF
 2009 So gesehen, Verkündi-gung (50x2min), Sat1
 2009 Abenteuer Wissen Piraten, Doku (30min), ZDF
 2008 Mission: Verbotene Stadt, Doku (45min), ZDF
 2008 Achternbusch, Doku (90min), BR, ORF
 2008 Klöster am Inn Gars, Doku (45min), BR
 2008 Klöster am Inn Stams, Doku (45min), BR
 2008 Klöster am Inn Au, Doku (45min), BR
 2008 Klöster am Inn Altötting, Doku (45min), BR
 2008 Das Geheimnis der Liturgie, Doku (45min), BR
 2008 Das Prinzip Hoffnung Enzyklika, Doku (45min), BR
 2008 1x1 des Rechts, Dokureihe (10x), BR-alpha
 2008 Paulus in Rom, Doku (45min), BR
 2008 1x1 der Wirtschaft, Dokureihe (10x), BR-alpha
 2007 Wunderkinder, Doku (90min), SWR
 2007 Heilige Orte Maria Zell, Doku (45min), BR, ORF
 2007 Heilige Orte Gößweinstein, Doku (45min), BR
 2007 Heilige Orte St. Wolfgang, Doku (45min), BR, ORF
 2007 Heilige Orte Neukirchen beim Heiligen Blut, Doku (45min), BR
 2007 Auf dem Jakobsweg mit Ulrich Reinthaler, Doku (45min), BR, ORF, 3sat
 2007 Jesus von Assisi, Doku (45min), ZDF
 2007 Das Jesus Foto, Doku (45min), ZDF
 2007 Kultur Geschichten Wohnen, Zeitrechnung, Fortbewegung, Lernen, Arbeit, Geld, Medizin, Kommunikation, Dokureihe (8x30min), BR-alpha
 2007 Kreuzwege Moosbach, Doku (45min), BR
 2007 Kreuzwege Heiligenkreuz, Doku (45min), BR
 2007 Benedikt in Bayern, Dokureihe (5x45min), BR
 2007 Wir sind Bischof, Doku (30min), ORF
 2007 Eine ganz normale Schule, Doku (30min), ORF
 2007 Blasphemie, Doku (45min), ORF
 2006 Willkommen Benedikt Marktl am Inn, Doku (45min), BR
 2006 Willkommen Benedikt Freising, Doku (45min), BR
 2006 Willkommen Benedikt München, Doku (45min), BR
 2006 Willkommen Benedikt Regensburg, Doku (45min), BR
 2006 Willkommen Benedikt Altötting, Doku (45min), BR
 2006 Heilige Orte Altötting, Doku (45min), BR, ORF
 2006 Heilige Orte Brikenstein, Doku (45min), BR, ORF
 2006 Heilige Orte Gurk, Doku (45min), BR, ORF
 2006 Heilige Orte Maria Plain, Doku (45min), BR, ORF
 2006 Klosterpio-niere Der leidenschaftliche König, Doku (45min), BR
 2006 Klosterpio-niere Die selbstbe-wusste Dienerin, Doku (45min), BR
 2006 Klosterpioniere Der ruhelose Mönch, Doku (45min), BR
 2006 Klosterpio-niere Der roman-tische Stahlbaron, Doku (45min), BR
 2006 Kaiphas und Pilatus, Doku (45min), ZDF
 2006 Karl Kraus, Doku (45min), ORF, BR
 2006 Paradiesgärten, Doku (52min), ARTE, ORF
 2006 Piero Marini, Doku (45min), BR-alpha
 2006 Caritas, Doku (45min), Caritas
 2005 Das Kreuz mit der Schrift, TV-Serie, BR-alpha
 2005 Mozart – Ich hätte München Ehre gemacht, TV-Film, BR
 2005 Der Kuss des Todes, Doku (45min), ZDF
 2005 Patient Landarzt, Doku (90min), SWR
 2005 So denkt der Papst, Doku (45min), ZDF
 2005 Petrus und die Päpste, Doku (45min), BR, ORF
 2005 Im Auftrag seiner Heiligkeit – Bischof Clemens in Rom, Doku (45min), BR
 2004 Reblaus, TV-Film, BR
 2004 Tatort: Nur ein Spiel, TV-Film (90min), BR
 2004 Ein Engel im Meer, Doku (45min), BR/WDR
 2004 Donauklöster Serbien, Doku (45min), BR, ORF
 2004 Donauklöster Ungarn, Doku (45min), BR, ORF
 2004 Donauklöster Slowakei, Doku (45Min), BR, ORF
 2004 Donauklöster Rumänien, Doku (45min), BR, ORF
 2004 Eine Hand voll Leben, Doku (45min), ZDF
 2004 König David und das Geheimnis des Tempels, Doku (45min), ZDF
 2004 Mythische Stätten Judentum in Israel, Doku (45min), BR
 2004 Schauen und Glauben, Dokureihe (15x), BR-alpha
 2003 Die Heilige Lanze, Doku (45min), ZDF
 2003 Judas, Doku (45min), ZDF
 2003 Hunger nach Orientierung, Doku (45min), ZDF
 2003 Herodes, Doku (45min), ZDF, Phoenix
 2003 ARD Buffet Stumbeckhof, Dokuserie (75x2min), SWR für ARD
 2002 Donauklöster Beuron, Doku (45min), BR
 2002 Daonauklöster Untermarchtal, Doku (45min), BR
 2002 Donauklöster, Doku (45min), BR
 2002 Donauklöster Schweiklberg, Doku (45min), BR
 2002 Donauklöster Wilhering, Doku (45min), BR
 2002 Donauklöster Baum-gartenberg, Doku (45min), BR
 2002 Donauklöster, Doku (45min), BR
 2002 Donauklöster Wien, Doku (45min), BR
 2002 Sixtina, Doku (45min), Tellux
 2002 Papst Johannes Paul II, Doku (45min), Tellux
 2002 Donauklöster Windberg, Doku (45min), ORF2, BR
 2002 Donauklöster Beuron, Doku (45min), BR
 2002 Donauklöster, Doku (45min), BR
 2002 Donauklöster, Doku (45min), BR
 2002 Donauklöster Schweiklberg, Doku (45min), BR
 2002 Donauklöster Wilhering, Doku (45min), BR
 2002 Donauklöster, Doku (45min), BR
 2002 Donauklöster, Doku (45min), BR
 2002 Donauklöster Wien, Doku (45min), BR
 2002 Sixtina, Doku (45min), Tellux
 2002 Papst Johannes Paul II, Doku (45min), Tellux
 2002 Donauklöster Windberg, Doku (45min), ORF2, BR
 2002 Donauklöster Metten, Doku (45min), ORF2, BR
 2002 Donauklöster Sankt Nikola, Doku (45min), BR, ORF
 2002 Donauklöster Engelszell, Doku (45min), ORF2
 2002 Donauklöster Sankt Florian, Doku (45min), ORF2, BR
 2002 Donauklöster Göttweig, Doku (45min), ORF2
 2001/2002 Donauklöster Weltenburg, Doku (45min), 3sat, BR, ORF2
 2001/2002 Donauklöster Melk, Doku (45min), 3sat, BR, ORF2
 2001/2002 Donauklöster Weltenburg, Doku (45min), 3sat, BR, ORF2
 2001/2002 Donauklöster Melk, Doku (45min), 3sat, BR, ORF2
 2001 Geheimnis des Fisches, Doku (52min), ZDF
 2001 Leben mit Mord-drohungen, Doku (30min), ZDF
 2001 Ausbildungsoffensive, Werbung (30sec), Werbe-agentur
 2001 Geliebtes Büro, Dokureihe (12x), BR-alpha
 2001 Aerospace, Magazin (12x), BR, BR- alpha, Discovery Channel, MDR
 2001 Geheimnis des Fisches, Doku (52min), ZDF
 2001 Leben mit Mord-drohungen, Doku (30min), ZDF
 2001 Ausbildung-soffensive, Werbung (30sec), Werbe-agentur
 2001 Geliebtes Büro, Dokureihe (12x), BR-alpha
 2001 Aerospace, Magazin (12x), BR, BR- alpha, Discovery Channel, MDR
 2000 Flucht über den Himalaya, Doku (30min), ZDF
 2000 Eremiten Wüsten-väter, Doku (52min), BR, ORF, BRF
 2000 Eremiten Einsiedeln, Doku (52min), BR, BR-ARTE, BRF
 2000 Treu im Kleinen, Doku (52 min), Tellux
 2000 Flucht über den Himalaya, Doku (30min), ZDF
 2000 Eremiten Wüsten-väter, Doku (52min), BR, ORF, BRF
 2000 Eremiten Einsiedeln, Doku (52min), BR, BR-ARTE, BRF
 2000 Treu im Kleinen, Doku (52 min), Tellux
 Ab 1999 Anschi und Karl Heinz, Magazin (über 100x15min), BR-alpha
 1998 Die Kranken Schwestern 27–34, TV-Serie, ORF
 1998 Die kranken Schwestern "Austrian Juke Box II", TV-Serie, Montreux98
 1997 Die kranken Schwestern 12–26, TV-Serie, ORF
 1996 Treffpunkt Kultur, virtuelle Filmtipps, TV-Serie, ORF
 1996 Die kranken Schwestern 1–11, TV-Serie, ORF
 1995 Padre Papa, TV-Spielfilm, SAT 1
 1995 Mali, TV-Spielfilm, BR
 1995 Subito 1–6, TV-Serie, ARD
 1994 Eine Frau mit Atmosphäre, TV-Spielfilm, ZDF
 1993 Nervenkrieg, TV-Spielfilm, ZDF
 1993 Lipstick, Kinospielfilm, Kino/Arte
 1998 "Lust auf Liebe" 32 Folgen, TV-Show, ORF
 1998 Wiener Stadtfest "Touch the Future – Stufe 1", Event, Verein Wr. Stadtfest
 1998 Die "Gull Night Show", TV – Late Night Show, Sternstunden
 1998 Die Männer der kranken Schwestern, TV – Special, ORF
 1998 Schluss mit Lustig, TV – Talk Comedy, ORF
 1998 Open House, Event, ÖVP
 1998 Meisterklasse – Wiener Volkstheater, Aufzeichnung, RM Production
 1998 1. Wiener Stadtspiel, Event, Verein Wr. Stadtfeste
 1997 TV-Wien – 90min, Lokalprogramme, Wien1
 1997 Reden wir übers Essen (40 Folgen), Magazin, Wien 1
 1997 Reden wir über die Nacht (40 Folgen), Talk-Magazin, Wien 1
 1997 Reden wir über die Anderen (50 Folgen), Talkshow, Wien 1
 1997 Reden wir im Café (50 Folgen), Talkshow, Wien 1
 1997 Reden wir über uns (40 Folgen), Talkmagazin, Wien 1
 1997 Reden wir über die Umgebung (40 Folgen), Magazin, Wien 1
 1997 Reden wir über Räder (40 Folgen), Info-Magazin, Wien 1
 1997 Reden wir über Rapid (40 Folgen), Fan-Magazin, Wien 1
 1997 Wien 1 – Quiz (200 Folgen), Spielshow, Wien 1
 1997 Reden wir über Wien (280 Folgen), Servicemagazin, Wien 1
 1997 Blind Videoclip, Musikvideo, BMG
 1997 Planet Media, Promotionfilm, Sony
 1997 Die Hektiker "Echt", Verkaufsvideo, Libro
 1996 Tausend Jahre Österreich, Installation, Hist.Museum
 1996 Das blonde Huhn (Bettina Soriat), CD, BMG
 1996 Mischa Maisky, Dokumentation, Arte
 1996 ÖVP Landesparteitag Wien, Veranstaltung, ÖVP
 1996 OEU – Österreich in Europa, Promotionfilm, Außenamt
 1996 ÖVP zur Europawahl, Belangsendung, ÖVP
 1995 La Nozze di Figaro, Salzburger Festspiele, Aufzeichnung, ORF
 1995 Nationalratswahl Berichterstattung ARD, TV-News, ARD
 1995 Jerusalem Wiener Staatsoper, Aufzeichnung, ORF
 1994 Das goldene Vlies (Burgtheater), Zuspielung, Burgtheater
 1994 EU Initialveranstaltung, Event, WK
 1994 Fitness 1–13, SitCom, ORF
 1994 Flower Power Flower, CD, BMG
 1994 Grüne Kinospot, Werbung, Grüne
 1994 So ist der Mensch, Installation, Hist.Museum
 1993 Mille Miglia (Pilot), Dokumentation,
 1993 Die lustige Witwe, Aufzeichnung, Unitel
 1993 Lipstick (Promotion CD), CD,
 1993 Austria On Air, CD, Ö-Werbung
 1993 Sternstunden (Sendungsentwicklung), Konsulent, BR
 1992 Das Käthchen von Heilbronn (Burgtheater), Zuspielung, Burgtheater

Publikationen
 2021: Notizen an Tobias: Gedanken eines Vaters zum Suizid seines Sohnes, Residenz-Verlag, Salzburg 2021, ISBN 978-3-7017-3514-3

Auszeichnungen (Auswahl)
 2021 Papageno-Medien-Sonderpreis
 2011 Grimme-Preis: Schnitzeljagd im Heiligen Land
 2009 Nominierung zum Deutschen Dokumentarfilmpreis: Achternbusch
 2002 Nominierung zum Deutschen Fernsehpreis: Flucht über den Himalaya
 2002 Special Jury Award BANFF: Flucht über den Himalaya
 2002 Romy: Donauklöster
 2001 Axel Springer Preis: Flucht über den Himalaya
 1997 Romy: Die kranken Schwestern
 1993 Diagonale Hauptpreis: Lipstick

Weblinks

 Verein zur Förderung eines selbstbestimmten Umgangs mit Medien

Einzelnachweise

Fernsehproduzent
Österreicher
Geboren 1965
Mann

redpajama_set_name: RedPajamaWikipedia


text:
SIDNEY KIWANIS CLUB
Kiwanis International®
Six Objects of Kiwanis
Sponsored Youth
Financial Support We Provide
Builders Club has an amazing January
January has been a busy month. Builder's Club members still continue to recycle paper and newspapers each week. They have partnered with ROI.
They have also been selling chocolate and roses to be delivered for Valentine's Day. This fundraiser will most likely benefit the Boys and Girls Club Teen Center. Ethan met with both 7th and 8th grade members and talked about the teen center. He asked for ideas, concerns, needs, and a wish list. There was a great discussion. Builders Club decided it would like to look into purchasing an item on the students wish list for the new Boys and Girls Club.
Builder's Club members also meet at least once a week to process plastic grocery bags to be repurposed into waterproof mats. There is a need for waterproof mats for refugees and a desire to keep all the bags out of the landfill. Students lay them out flat and then cut off the tops and bottoms. The middle of the bags are tied together to make "playarn" (plastic yarn). They are then weaved to make mats. The tops and bottom of the bags are also used to stuff pillows or stuffed animals. Our students are just processing the bags. After processing here, the bags will be taken to a humanitarian center in Salt Lake City where they will be made into mats. The mats made from the bags our students process will go to Syria and the mountains of Ecuador.
Builder's Club applied money raised in October to benefit the Richland County Library. Mrs. Allen contacted Kelly Reisig at the library and asked if the club could purchase youth adult books. They asked for their "wish list" and for missing books or books needed to complete series. They gave the club a list of 19 books and the club purchased them. When the books come in, the students will go to the library and help them process them.
Miss Montana visits Builders Club, promotes Own Your Movement initiative
[Photo credits: Kelly Johnson]
Miss Montana 2018 visited one of our sponsored youth organizations yesterday. Laura Haller brought her positive message to Builders Club members in Sidney Middle School.
During Laura's year of service as Miss Montana, Laura is working closely with the only Children's Miracle Network Hospital in Montana, Shodair Children's Hospital. She is also advocating for her social impact initiative, Own Your Movement, during her Crown to Classroom Tour. Using narrative and lessons she learned from her life as a professional dancer, pre-medical student, marathon runner, triathlete, small business owner, and world traveler, she hopes to inspire Montana children to get up and get moving so they have the ability to follow their passions in life.
Get up and get moving. What a joyful and constructive message!
Laura says, representing Montana as Miss Montana 2018 is her proudest achievement, and she looks forward to sharing her passion for health and wellness while also advocating for fearlessly living life to its full potential.
That's saying quite a bit when you learn more about her background. Miss Montana 2018, Laura Halter, was born in the beautiful mountains of western Montana. She began her professional dancing career at the age of 18 in the Northwest as a classical ballet dancer. While dancing professionally full-time, she also attended Boise State University on an academic scholarship with aspirations to become a medical doctor for women's health. She graduated cum laude from Boise State University in 2016 with a Bachelor of Science Degree in Medical/Health Sciences and a Minor in Dance. She was then hired as the principal professional dancer with Viking Ocean Cruises, where she had the opportunity to dance and travel to over 30 countries and 5 continents. After spending over a year at sea, Laura competed for the prestigious position of Miss Montana, and won the title of Miss Montana 2018. She recently competed in Miss America and won both a talent and STEM (Science, Technology, Engineering, and Math) scholarship. She is the first Miss Montana to ever receive the STEM scholarship.
Apple Sale
Builders Club
ELIMINATE Project
Fund Raisers
Montana Behavior Initiative
Pie Social
Ticket Taking
Home | Kiwanis International | Six Objects | Our Club | Projects | Sponsored Youth | Newsletters | Blog | Gallery | Contact
Copyright © 2018-2019 Kiwanis Club of Sidney, Montana


text:
Chalaca
Thursday, May 9, 7:30 pm
300 2nd St SE
Now in its sixth season, Schubert Club Mix is an innovative series that takes the formality out of classical music. Audiences are treated to remarkable and intimate performances with relevant artists who are influencing the musical landscape of today.
A relatively new ensemble (formed in 2016), Chalaca explores the confluence of cultures found in South America and the Caribbean with a unique combination of clarinet, harp, and percussion. Following the migration of rhythm from Africa and Europe, to the Andean Mountains, to the Amazon…and finally, right to the heart of America, Chalaca is a celebration of the composers who have immigrated to the United States from Argentina, Brazil, Colombia, Cuba, Puerto Rico, and Venezuela…alongside the folk masters who inspired them.
All concerts general admission.
Bridget Kibbey, harp
Samuel Torres, percussion
Gabriel Campos Zamora, clarinet
About Machine Shop
The Pillsbury A-Mill was once the largest working mill in the world, and this building was an integral part of its success. State of the art, modern equipment was produced and repaired there. Reopened in 2016, this historic machinery shop has been carefully restored, keeping the original 1916 architectural details intact, while introducing modern luxury in this industrial space. Just as the Pillsbury machine shop was an important player in establishing Minneapolis, Machine Shop Historic Venue is cornerstone for the city of Minneapolis, as a host of extraordinary and glamorous events.
Full-Season Packages
Save $5 per concert when you buy a full-season six-concert package.
Purchase a Full-Season Package
Pick-Three Packages
Save $2 per concert when you buy a pick-three package.
Purchase a Pick-Three Package


Wow. The Millenium is a beautiful boat with a large central area and covered back deck. We meet our fellow boat-mates, some who have unfortunately not yet gotten their sea legs, and hear about the plans for our first day. We hear (for the first time of many!) that some things are 'endemic' to the Galapagos, and understand the importance of this.
Santa Fe, our first island, is like an alien world. The unusual cactus trees, not to mention the huge land iguanas that we see, are amazing. And then we see... SEA LIONS! We get up close and personal with some on the beach, who are unperturbed by our presence. We find out that some are big posers for the camera! The big beach master sea lion however, lets us know that we do have limits on his beach! We snorkel and play follow the leader with a friendly sea lion who enjoys copying our spins in the water and pulling on our fins!
South Plaza - yet another alien world. (and more sea lions!) The colors of the ground cover are so vibrant and along the paths are smaller bright iguanas. The sea birds along the cliff are amazing to watch and we find a group of 'bachelor' sea lions who bear a remarkable resemblance to a bunch of guys hanging out together on the edge of the cliff.
Now back to the Millenium for more great food and company!