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Introduction: The A2A adenosine receptor (A2AAR) is expressed in brain, vasculature and immune cells. According to the alterations of the A2AAR expression in multiple diseases, it is a highly attractive diagnostic and therapeutic target. We developed the A2AAR-specific PET radiotracer [18F]FLUDA and investigated it in healthy mice and piglets, in a rotenone-based mouse model of Parkinson’s disease (RMMPD) and in transgenic mice overexpressing the human A2AAR in heart (TG) [1 3]. Methods: On the basis of a one-pot two-step radiofluorination procedure, a remotely controlled automated radiosynthesis of [18F]FLUDA using the TRACERlab FX2N synthesis module was developed. In vitro autoradiography was performed with cryosections of tissue from animal models. In vivo stability was investigated in mouse by radio-HPLC analyses of blood plasma and brain homogenates. The biodistribution was investigated by dynamic PET/MR studies in healthy mice and piglets under control and blocking conditions (vehicle vs. blocking with 2.5 mg/kg tozadenant and/or 1.0 mg/kg istradefylline) and in both mouse models. The binding potential (BPND) in vivo was calculated using the simplified reference tissue modelling with the cerebellum as reference region. A single dose acute toxicity study was performed in Wistar rats according to the ICH guideline M3(R2). PET-derived radiation dosimetry was estimated in piglets. Results: A reliable and reproducible procedure for the automated production of [18F]FLUDA was successfully established (Fig. 1A) [4]. In vitro autoradiography revealed highly selective binding and high affinity of [18F]FLUDA towards the A2AAR of the three species (KD values 0.7-5.9 nM, Fig. 1B). At 15 min after i.v. injection of [18F]FLUDA in mice, the parent fraction accounted for about 100% in brain and 71% in plasma. PET studies confirmed the specific binding of [18F]FLUDA in vivo to the striatal A2AAR in mice and piglets (BPND=3.9 and 1.3, Fig. 1C). The availability of A2AAR in the P

Introduction: The A2A adenosine receptor (A2AAR) is expressed in brain, vasculature and immune cells. According to the alterations of the A2AAR expression in multiple diseases, it is a highly attractive diagnostic and therapeutic target. We developed the A2AAR-specific PET radiotracer [18F]FLUDA and investigated it in healthy mice and piglets, in a rotenone-based mouse model of Parkinson’s disease (RMMPD) and in transgenic mice overexpressing the human A2AAR in heart (TG) [1 3]. Methods: On the basis of a one-pot two-step radiofluorination procedure, a remotely controlled automated radiosynthesis of [18F]FLUDA using the TRACERlab FX2N synthesis module was developed. In vitro autoradiography was performed with cryosections of tissue from animal models. In vivo stability was investigated in mouse by radio-HPLC analyses of blood plasma and brain homogenates. The biodistribution was investigated by dynamic PET/MR studies in healthy mice and piglets under control and blocking conditions (vehicle vs. blocking with 2.5 mg/kg tozadenant and/or 1.0 mg/kg istradefylline) and in both mouse models. The binding potential (BPND) in vivo was calculated using the simplified reference tissue modelling with the cerebellum as reference region. A single dose acute toxicity study was performed in Wistar rats according to the ICH guideline M3(R2). PET-derived radiation dosimetry was estimated in piglets. Results: A reliable and reproducible procedure for the automated production of [18F]FLUDA was successfully established (Fig. 1A) [4]. In vitro autoradiography revealed highly selective binding and high affinity of [18F]FLUDA towards the A2AAR of the three species (KD values 0.7-5.9 nM, Fig. 1B). At 15 min after i.v. injection of [18F]FLUDA in mice, the parent fraction accounted for about 100% in brain and 71% in plasma. PET studies confirmed the specific binding of [18F]FLUDA in vivo to the striatal A2AAR in mice and piglets (BPND=3.9 and 1.3, Fig. 1C). The availability of A2AAR in the P

The cerebral expression of the A2A adenosine receptor (A2AAR) is altered in neurodegenerative disorders diseases such as Parkinson's (PD) or Huntington’s (HD) diseases, making these recep-tors an attractive diagnostic and therapeutic target. We aimed to further investigate the pharma-cokinetic properties in the brain of our recently developed A2AAR specific antagonist radioligand [18F]FLUDA. For this purpose, we retrospectively analysed dynamic PET studies of healthy mice and rotenone-treated mice, and undertook dynamic PET studies with healthy pigs. We performed analysis of mouse brain time-activity curves to calculate the mean residence time (MRT) by non-compartmental analysis and the binding potential (BPND) of [18F]FLUDA using the simplified reference tissue model (SRTM). For the pig studies, we performed a Logan graphical analysis to calculate the radiotracer distribution volume (VT) at baseline and under blocking conditions with tozadenant. The MRT of [18F]FLUDA in the striatum of mice was decreased by 30 % after treatment with the A2AAR antagonist, istradefylline. Mouse results showed the highest BPND (3.9 to 5.9) in the striatum. SRTM analysis showed a 20% lower A2AAR availability in the rotenone-treated mice compared to the control-aged group. Tozadenant treatment significantly decreased the VT (14.6 vs. 8.5 mL · g-1) and BPND values (1.3 vs. 0.3) in pig striatum. This study confirms the target specificity and a high BPND of [18F]FLUDA in the striatum. We conclude that [18F]FLUDA is a suitable tool for the non-invasive quantitation by PET of altered A2AAR expression in neurodegenerative diseases such as PD and HD.

Introduction: Selective A₂AR antagonists have emerged as potential therapeutics for multiple diseases. With regard to Parkinson’s disease, adjunctive treatment of A₂AR antagonists potentially reduces adverse effects of long-term L-DOPA treatment. Therefore, imaging of receptor availability during the A2AR-tailored therapy is of utmost importance. We recently developed [¹⁸F]FLUDA as an novel A₂AR-specific PET radiotracer [1]. Methods: [¹⁸F]FLUDA was synthesized by an automated procedure Biological evaluation was performed in healthy mice and piglets. In vitro autoradiography was performed with brain cryosections. In vivo metabolism was analysed by radio-HPLC of plasma and brain homogenate. Pharamcokinetics and biodistribution was assessed by dynamic PET imaging under control and blocking conditions (2.5 mg/kg tozadenant and/or 1.0 mg/kg istradefylline). SUV ratio (SUVr) of striatum-over-cerebellum was used as a metric for specific uptake. A single dose acute toxicity study was performed in Wistar rats according to the ICH guideline M3(R2). Radiation dosimetry was investigated in piglets. Results: In vitro autoradiography revealed an A₂AR affinity (KD;) of 4.3 and 0.7 nM and an A₂AR density (Bmax) of 556 and 218 fmol/mg in the striatum of mice and piglets. No radiometabolites were detected in the mouse brain at 15 min p.i., whereas radiometabolites were found in piglet plasma but are assumed to not cross the blood-brain barrier. PET demonstrated high specific binding of [¹⁸F]FLUDA in both species (Fig.1). Toxicity studies revealed no adverse effects up to a dose of 30 µg/kg (~4000-fold of expected human dose). The ED to humans is 16.4 µSv/MBq, which is in the range of other ¹⁸F-labeled radiotracers [2]. Conclusion: We have demonstrated that [¹⁸F]FLUDA is suitable for determination of the A₂AR availability in the striatum. No safety concerns are expected upon administration of [¹⁸F]FLUDA according to toxicity and dosimetry data. These results encourage the clinical tra

Introduction: Selective A₂AR antagonists have emerged as potential therapeutics for multiple diseases. With regard to Parkinson’s disease, adjunctive treatment of A₂AR antagonists potentially reduces adverse effects of long-term L-DOPA treatment. Therefore, imaging of receptor availability during the A2AR-tailored therapy is of utmost importance. We recently developed [¹⁸F]FLUDA as an novel A₂AR-specific PET radiotracer [1]. Methods: [¹⁸F]FLUDA was synthesized by an automated procedure Biological evaluation was performed in healthy mice and piglets. In vitro autoradiography was performed with brain cryosections. In vivo metabolism was analysed by radio-HPLC of plasma and brain homogenate. Pharamcokinetics and biodistribution was assessed by dynamic PET imaging under control and blocking conditions (2.5 mg/kg tozadenant and/or 1.0 mg/kg istradefylline). SUV ratio (SUVr) of striatum-over-cerebellum was used as a metric for specific uptake. A single dose acute toxicity study was performed in Wistar rats according to the ICH guideline M3(R2). Radiation dosimetry was investigated in piglets. Results: In vitro autoradiography revealed an A₂AR affinity (KD;) of 4.3 and 0.7 nM and an A₂AR density (Bmax) of 556 and 218 fmol/mg in the striatum of mice and piglets. No radiometabolites were detected in the mouse brain at 15 min p.i., whereas radiometabolites were found in piglet plasma but are assumed to not cross the blood-brain barrier. PET demonstrated high specific binding of [¹⁸F]FLUDA in both species (Fig.1). Toxicity studies revealed no adverse effects up to a dose of 30 µg/kg (~4000-fold of expected human dose). The ED to humans is 16.4 µSv/MBq, which is in the range of other ¹⁸F-labeled radiotracers [2]. Conclusion: We have demonstrated that [¹⁸F]FLUDA is suitable for determination of the A₂AR availability in the striatum. No safety concerns are expected upon administration of [¹⁸F]FLUDA according to toxicity and dosimetry data. These results encourage the clinical tra

Purpose: The adenosine A2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A2A receptor radiotracer and report herein the preclinical evaluation of [18F]FLUDA, a deuterated isotopologue of [18F]FESCH. Methods: [18F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats. Results: [18F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72 180 GBq/µmol. Autoradiography proved A2A receptor-specific accumulation of [18F]FLUDA in the striatum of mouse and pig brain. In vivo evaluation in mice revealed improved stability of [18F]FLUDA compared to [18F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [18F]FLUDA towards striatal A2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 µg/kg, ~ 4000-fold the dose applied in human PET studies using [18F]FLUDA. Conclusions: The new radiotracer [18F]FLUDA is suitable to detect the availability of the A2A receptor in the brain with high target specificity. It is regarded ready for human application.

Pridopidine is an investigational drug in late stage development for the treatment of Huntington disease and originally postulated to act as dopamine stabilizer by modulating dopamine-dependent motor behavior. However, preclinical studies show pridopidine has highest affinity to sigma-1 receptors. Importantly, mediated by sigma-1 receptors, pridopidine has neuroprotective properties and enhances neuronal plasticity. The aim of our study was to determine the in-vivo the target engagement (receptor occupancy) of pridopidine at clinically relevant doses in healthy volunteers and Huntington disease patients. We used sigma-1 receptor-specific (S)-(-)-[18F]Fluspidine and dopamine D2/D3 receptor-specific [18F]Fallypride PET imaging to quantify the sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine. Eleven male healthy volunteers (pridopidine 0.5 to 90 mg in six dose groups) and three male Huntington disease patients (pridopidine 90 mg) were studied twice before and 2h following single oral doses of pridopidine using S-(-)-[18F]Fluspidine PET (300 MBq, 0-90min p.i.). Distribution volume VT was quantified using kinetic modeling (One-tissue compartment model; metabolite correction). Four male healthy volunteers were studied twice using [18F]Fallpride PET (200 MBq, 0-210min p.i.) before and 2h after a single oral dose of pridopidine (90 mg). Binding potential BPND was assessed by the simplified reference model. Volume-of-interest analyses were performed. For each subject/tracer, the receptor occupancy was calculated by the Lassen plot analysis. In healthy volunteers, there was high sigma-1 receptor occupancy (87 to 91%) across all brain regions at doses ranging from 22.5 to 90 mg. The sigma-1 receptor occupancy was 43% at 1 mg pridopidine. In Huntington disease patients, very similar to healthy volunteers, at 90 mg pridopidine, there was high sigma-1 receptor occupancy (87±7%, n.s.). In contrast, in healthy volunteers, there was only negligible dopamine D2/D3 recepto

Introduction: Selective A₂AR antagonists have emerged as potential therapeutics for multiple diseases. With regard to Parkinson’s disease, adjunctive treatment of A₂AR antagonists potentially reduces adverse effects of long-term L-DOPA treatment. Therefore, imaging of receptor availability during the A2AR-tailored therapy is of utmost importance. We recently developed [¹⁸F]FLUDA as an novel A₂AR-specific PET radiotracer [1]. Methods: [¹⁸F]FLUDA was synthesized by an automated procedure Biological evaluation was performed in healthy mice and piglets. In vitro autoradiography was performed with brain cryosections. In vivo metabolism was analysed by radio-HPLC of plasma and brain homogenate. Pharamcokinetics and biodistribution was assessed by dynamic PET imaging under control and blocking conditions (2.5 mg/kg tozadenant and/or 1.0 mg/kg istradefylline). SUV ratio (SUVr) of striatum-over-cerebellum was used as a metric for specific uptake. A single dose acute toxicity study was performed in Wistar rats according to the ICH guideline M3(R2). Radiation dosimetry was investigated in piglets. Results: In vitro autoradiography revealed an A₂AR affinity (KD;) of 4.3 and 0.7 nM and an A₂AR density (Bmax) of 556 and 218 fmol/mg in the striatum of mice and piglets. No radiometabolites were detected in the mouse brain at 15 min p.i., whereas radiometabolites were found in piglet plasma but are assumed to not cross the blood-brain barrier. PET demonstrated high specific binding of [¹⁸F]FLUDA in both species (Fig.1). Toxicity studies revealed no adverse effects up to a dose of 30 µg/kg (~4000-fold of expected human dose). The ED to humans is 16.4 µSv/MBq, which is in the range of other ¹⁸F-labeled radiotracers [2]. Conclusion: We have demonstrated that [¹⁸F]FLUDA is suitable for determination of the A₂AR availability in the striatum. No safety concerns are expected upon administration of [¹⁸F]FLUDA according to toxicity and dosimetry data. These results encourage the clinical tra

Introduction: Selective A₂AR antagonists have emerged as potential therapeutics for multiple diseases. With regard to Parkinson’s disease, adjunctive treatment of A₂AR antagonists potentially reduces adverse effects of long-term L-DOPA treatment. Therefore, imaging of receptor availability during the A2AR-tailored therapy is of utmost importance. We recently developed [¹⁸F]FLUDA as an novel A₂AR-specific PET radiotracer [1]. Methods: [¹⁸F]FLUDA was synthesized by an automated procedure Biological evaluation was performed in healthy mice and piglets. In vitro autoradiography was performed with brain cryosections. In vivo metabolism was analysed by radio-HPLC of plasma and brain homogenate. Pharamcokinetics and biodistribution was assessed by dynamic PET imaging under control and blocking conditions (2.5 mg/kg tozadenant and/or 1.0 mg/kg istradefylline). SUV ratio (SUVr) of striatum-over-cerebellum was used as a metric for specific uptake. A single dose acute toxicity study was performed in Wistar rats according to the ICH guideline M3(R2). Radiation dosimetry was investigated in piglets. Results: In vitro autoradiography revealed an A₂AR affinity (KD;) of 4.3 and 0.7 nM and an A₂AR density (Bmax) of 556 and 218 fmol/mg in the striatum of mice and piglets. No radiometabolites were detected in the mouse brain at 15 min p.i., whereas radiometabolites were found in piglet plasma but are assumed to not cross the blood-brain barrier. PET demonstrated high specific binding of [¹⁸F]FLUDA in both species (Fig.1). Toxicity studies revealed no adverse effects up to a dose of 30 µg/kg (~4000-fold of expected human dose). The ED to humans is 16.4 µSv/MBq, which is in the range of other ¹⁸F-labeled radiotracers [2]. Conclusion: We have demonstrated that [¹⁸F]FLUDA is suitable for determination of the A₂AR availability in the striatum. No safety concerns are expected upon administration of [¹⁸F]FLUDA according to toxicity and dosimetry data. These results encourage the clinical tra

Overexpression of monocarboxylate transporters (MCTs) has been shown for a variety of human cancers (e.g. colon, brain, breast, and kidney) and inhibition resulted in intracellular lactate accumulation, acidosis and cell death. Thus, MCTs are promising targets to investigate tumor cancer metabolism with positron emission tomography (PET). Here, the organ doses (OD) and the effective dose (ED) of the first 18F-labeled MCT1/MCT4 inhibitor were estimated in juvenile pigs. Whole-body dosimetry was performed in three piglets (age: ~6 weeks, weight: ~13-15 kg). The animals were anaesthetized and subjected to sequential PET/CT up to 5h after i.v. injection of 156 ± 54 MBq [18F]FACH. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity data. Time and mass scales were adapted to the human order of magnitude and the ODs calculated using the ICRP 89 adult male phantom with OLINDA 2.1. The ED was calculated using tissue weighting factors as published in the ICRP103. The highest organ dose was received by the urinary bladder (62.6 ± 28.9 µSv/MBq), followed by the gall bladder(50.4 ± 37.5 µSv/MBq) and the pancreas (30.5 ± 27.3 µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.5 ± 1.1 µSv/MBq) followed by the red marrow (1.7 ± 0.3 µSv/MBq) and the stomach (1.3 ± 0.4 µSv/MBq). According to this preclinical analysis,the ED to humans is 12.4 µSv/MBq when applying the ICRP103 tissue weighing factors. Taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%, the conversion factor applied for estimation of the ED to humans would raise to 20.6 µSv/MBq. Resultantly, the ED to humans upon an i.v. application of ~300 MBq [18F]FACH would be about 6.2mSv. This risk assessment encourages to translate [18F]FACH to clinical study phases and to further investigate its potential as a clinical tool for cancer imaging with PET.

What did the early Greek philosophers think about animals and their lives? How did they view plants? And, ultimately, what type of relationship did they envisage between all sorts of living beings? On these topics there is evidence of a prolonged investigation by several Presocratics. However, scholarship has paid little attention to these issues and to the surprisingly "modern" development they received in Presocratics' doctrines. This book fills this lacuna through a detailed (and largely unprecedented) analysis of the extant evidence. The volume includes also the first extensive collection of the ancient sources pertaining to living beings and life in early Greek philosophy, organized chronologically and thematically.

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tubingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we ar

© 2018 Elsevier B.V. Through litter decomposition enormous amounts of carbon is emitted to the atmosphere. Numerous large-scale decomposition experiments have been conducted focusing on this fundamental soil process in order to understand the controls on the terrestrial carbon transfer to the atmosphere. However, previous studies were mostly based on site-specific litter and methodologies, adding major uncertainty to syntheses, comparisons and meta-analyses across different experiments and sites. In the TeaComposition initiative, the potential litter decomposition is investigated by using standardized substrates (Rooibos and Green tea) for comparison of litter mass loss at 336 sites (ranging from −9 to +26 °C MAT and from 60 to 3113 mm MAP) across different ecosystems. In this study we tested the effect of climate (temperature and moisture), litter type and land-use on early stage decomposition (3 months) across nine biomes. We show that litter quality was the predominant controlling factor in early stage litter decomposition, which explained about 65% of the variability in litter decomposition at a global scale. The effect of climate, on the other hand, was not litter specific and explained <0.5% of the variation for Green tea and 5% for Rooibos tea, and was of significance only under unfavorable decomposition conditions (i.e. xeric versus mesic environments). When the data were aggregated at the biome scale, climate played a significant role on decomposition of both litter types (explaining 64% of the variation for Green tea and 72% for Rooibos tea). No significant effect of land-use on early stage litter decomposition was noted within the temperate biome. Our results indicate that multiple drivers are affecting early stage litter mass loss with litter quality being dominant. In order to be able to quantify the relative importance of the different drivers over time, long-term studies combined with experimental trials are needed.

Der Abstract wird nachgereicht.

Ziel: Vor erstmaliger Anwendung neuartiger Radiopharmaka im Menschen muss präklinisch eine Abschätzung der inneren Strahlenexposition des Menschen am Tiermodell erfolgen. Hierfür stehen computergenerierte VOXEL Phantome (VP) unterschiedlicher Tiermodelle zur Verfügung. Die Verschiedenen, teils regulatorisch für die klinische Anwendung zugelassenen Softwaretools für die Inkorporationsdosimetrie nutzen Implementationen dieser VP für die präklinische und klinische Dosimetrie. Basierend auf den anatomischen und geometrischen Verhältnissen enthalten die VP die in Zielorganen und Organsystemen absorbierte spezifische Fraktion der von Quellorganen ausgehenden/emittierten Strahlenenergie (specific absorbed fraction, SAF). Diese sind grundlegend für die in Organen und Organsystemen absorbierten Dosis (OD) nach dem MIRD Schema und werden durch Monte-Carlo-Simulation (MC) berechnet. Eigene Arbeiten haben gezeigt, dass im Vergleich zur Verwendung von Kleintieren mit Ferkeln eine den Verhältnissen am Menschen vergleichbarere Abschätzung der Strahlenexposition möglich ist. Daher wurde ein VP für Ferkel erstellt und dessen SAFs durch MC berechnet. Methodik: Ein 12 kg Ferkel (8 Wochen) wurde nach i.v. Injektion von [18F]Flubatine (185.4 MBq) bis zu 4,5 h p.i. in einem PET/CT (SIEMENS Biograph 16) gemessen und die List-Mode Daten nach Standardkorrekturen rekonstruiert. Unter Nutzung der PET bzw. CT Daten und der Software ROVER (ABX, Radeberg) wurden 18 Organe vorwiegend manuell segmentiert und als DICOM Structure Set exportiert. Mit der Software OEDIPE [1] erfolgte die Zuordnung der Gewebeeigenschaften der segmentierten Organe nach ICRU [2]. Anschließend erfolgt die Simulation in MCNPX (v.2.6.0) mit 20 Millionen Events als Abbruchkriterium. Ergebnisse: Mit OEDIPE gelingt unter Verwendung des Ergebnisses der MC-Simulation die Erzeugung der SAFs für ein VP des Ferkels. Für 28 Radionuklide wurden SAFs (mGy/MBq*s) für Gehirn, Leber, Gallenblase, Nieren, Dünn- und Dickdarm, Lunge, Herz

Ziel: Bei der Translation neuartiger Radiotracer in die klinische Phase ist eine Abschätzung der Strahlenexposition vor Erstanwendung am Menschen notwendig. Hierbei werden die Organdosen (OD) sowie die effektive Dosis (ED) am Tiermodell abgeschätzt, welche nach i.v. Injektion eines Radiotracers entstehen. Erstmalig wurde Kleintier-PET/MRT zur rein bildgebungsbasierten Inkorporationsdosimetrie mit CD-1 Mäusen eingesetzt. Um den Einfluss von Speziesunterschieden zu untersuchen wurden PET/CT-Studien an Ferkeln durchgeführt und die Ergebnisse mit am Menschen erhobenen Ergebnissen (PET/CT) verglichen. Methodik: Nach i.v. Injektion von (-)- oder (+)-[18F]Flubatine (a, b) bzw. (S)- oder (R)-[18F]Fluspidine (c,d) wurden (i) In-vivo-PET/MRT- (MEDISO nanoScan, Budapest) und PET/CT-Scans (SIEMENS Biograph 16) bis zu 7 h p.i. durchgeführt, die List-Mode Daten unter Nutzung der Standardkorrekturen rekonstruiert und die Organaktivitäten (OA) mit ROVER (ABX, Radeberg) bestimmt; (ii) (a, c, d) Ex-vivo-Organentnahme an Mäusen und Messung der OA in einem Gammacounter durchgeführt (Goldstandard). Nach Extrapolation der Tierdaten auf menschliche Verhältnisse, wurden die OD und die ED mit OLINDA für 3 Spezies berechnet. Ergebnisse: Die Dosimetrie für a/b ergab eine ED (µSv/MBq) von 12,5/12,1 (30 Mäuse), 13,4/14,3 (8 Ferkel), 22,3/23,0 (n=6 Menschen) und für (c/d) 12,9/14,0 (6 Mäuse), 21,0/n.a. (4 Menschen). Während a und b eine vergleichbare Biokinetik sowie ED zeigen, ist die ED von c und d signifikant (p=0,025) verschieden basierend auf Enantiomeren Unterschieden. Weiterhin zeigt sich eine Unterschätzung der ED erhoben mit Tierdaten im Vergleich zum Menschen von 38% (Ferkel) bis 47% (Mäuse). Schlussfolgerung: Die Strahlenexposition nach i.v. Applikation von a,b,c,d liegt im Bereich der durch andere F-18-markierter Radiotracer. Die Abschätzung der ED unter Nutzung von Tiermodellen mit Hilfe eines Kleintier-PET/MRT ist unter Berücksichtigung der genannten Limitationen möglich und liefer

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we ar

Ziel: Vor erstmaliger Anwendung neuartiger Radiopharmaka im Menschen muss präklinisch eine Abschätzung der inneren Strahlenexposition des Menschen am Tiermodell erfolgen. Hierfür stehen computergenerierte VOXEL Phantome (VP) unterschiedlicher Tiermodelle zur Verfügung. Die Verschiedenen, teils regulatorisch für die klinische Anwendung zugelassenen Softwaretools für die Inkorporationsdosimetrie nutzen Implementationen dieser VP für die präklinische und klinische Dosimetrie. Basierend auf den anatomischen und geometrischen Verhältnissen enthalten die VP die in Zielorganen und Organsystemen absorbierte spezifische Fraktion der von Quellorganen ausgehenden/emittierten Strahlenenergie (specific absorbed fraction, SAF). Diese sind grundlegend für die in Organen und Organsystemen absorbierten Dosis (OD) nach dem MIRD Schema und werden durch Monte-Carlo-Simulation (MC) berechnet. Eigene Arbeiten haben gezeigt, dass im Vergleich zur Verwendung von Kleintieren mit Ferkeln eine den Verhältnissen am Menschen vergleichbarere Abschätzung der Strahlenexposition möglich ist. Daher wurde ein VP für Ferkel erstellt und dessen SAFs durch MC berechnet. Methodik: Ein 12 kg Ferkel (8 Wochen) wurde nach i.v. Injektion von [18F]Flubatine (185.4 MBq) bis zu 4,5 h p.i. in einem PET/CT (SIEMENS Biograph 16) gemessen und die List-Mode Daten nach Standardkorrekturen rekonstruiert. Unter Nutzung der PET bzw. CT Daten und der Software ROVER (ABX, Radeberg) wurden 18 Organe vorwiegend manuell segmentiert und als DICOM Structure Set exportiert. Mit der Software OEDIPE [1] erfolgte die Zuordnung der Gewebeeigenschaften der segmentierten Organe nach ICRU [2]. Anschließend erfolgt die Simulation in MCNPX (v.2.6.0) mit 20 Millionen Events als Abbruchkriterium. Ergebnisse: Mit OEDIPE gelingt unter Verwendung des Ergebnisses der MC-Simulation die Erzeugung der SAFs für ein VP des Ferkels. Für 28 Radionuklide wurden SAFs (mGy/MBq*s) für Gehirn, Leber, Gallenblase, Nieren, Dünn- und Dickdarm, Lunge, Herz

Ziel: Bei der Translation neuartiger Radiotracer in die klinische Phase ist eine Abschätzung der Strahlenexposition vor Erstanwendung am Menschen notwendig. Hierbei werden die Organdosen (OD) sowie die effektive Dosis (ED) am Tiermodell abgeschätzt, welche nach i.v. Injektion eines Radiotracers entstehen. Erstmalig wurde Kleintier-PET/MRT zur rein bildgebungsbasierten Inkorporationsdosimetrie mit CD-1 Mäusen eingesetzt. Um den Einfluss von Speziesunterschieden zu untersuchen wurden PET/CT-Studien an Ferkeln durchgeführt und die Ergebnisse mit am Menschen erhobenen Ergebnissen (PET/CT) verglichen. Methodik: Nach i.v. Injektion von (-)- oder (+)-[18F]Flubatine (a, b) bzw. (S)- oder (R)-[18F]Fluspidine (c,d) wurden (i) In-vivo-PET/MRT- (MEDISO nanoScan, Budapest) und PET/CT-Scans (SIEMENS Biograph 16) bis zu 7 h p.i. durchgeführt, die List-Mode Daten unter Nutzung der Standardkorrekturen rekonstruiert und die Organaktivitäten (OA) mit ROVER (ABX, Radeberg) bestimmt; (ii) (a, c, d) Ex-vivo-Organentnahme an Mäusen und Messung der OA in einem Gammacounter durchgeführt (Goldstandard). Nach Extrapolation der Tierdaten auf menschliche Verhältnisse, wurden die OD und die ED mit OLINDA für 3 Spezies berechnet. Ergebnisse: Die Dosimetrie für a/b ergab eine ED (µSv/MBq) von 12,5/12,1 (30 Mäuse), 13,4/14,3 (8 Ferkel), 22,3/23,0 (n=6 Menschen) und für (c/d) 12,9/14,0 (6 Mäuse), 21,0/n.a. (4 Menschen). Während a und b eine vergleichbare Biokinetik sowie ED zeigen, ist die ED von c und d signifikant (p=0,025) verschieden basierend auf Enantiomeren Unterschieden. Weiterhin zeigt sich eine Unterschätzung der ED erhoben mit Tierdaten im Vergleich zum Menschen von 38% (Ferkel) bis 47% (Mäuse). Schlussfolgerung: Die Strahlenexposition nach i.v. Applikation von a,b,c,d liegt im Bereich der durch andere F-18-markierter Radiotracer. Die Abschätzung der ED unter Nutzung von Tiermodellen mit Hilfe eines Kleintier-PET/MRT ist unter Berücksichtigung der genannten Limitationen möglich und liefer

Der Abstract wird nachgereicht.

Der Abstract wird nachgereicht.

Ziel: Vor erstmaliger Anwendung neuartiger Radiopharmaka im Menschen muss präklinisch eine Abschätzung der inneren Strahlenexposition des Menschen am Tiermodell erfolgen. Hierfür stehen computergenerierte VOXEL Phantome (VP) unterschiedlicher Tiermodelle zur Verfügung. Die Verschiedenen, teils regulatorisch für die klinische Anwendung zugelassenen Softwaretools für die Inkorporationsdosimetrie nutzen Implementationen dieser VP für die präklinische und klinische Dosimetrie. Basierend auf den anatomischen und geometrischen Verhältnissen enthalten die VP die in Zielorganen und Organsystemen absorbierte spezifische Fraktion der von Quellorganen ausgehenden/emittierten Strahlenenergie (specific absorbed fraction, SAF). Diese sind grundlegend für die in Organen und Organsystemen absorbierten Dosis (OD) nach dem MIRD Schema und werden durch Monte-Carlo-Simulation (MC) berechnet. Eigene Arbeiten haben gezeigt, dass im Vergleich zur Verwendung von Kleintieren mit Ferkeln eine den Verhältnissen am Menschen vergleichbarere Abschätzung der Strahlenexposition möglich ist. Daher wurde ein VP für Ferkel erstellt und dessen SAFs durch MC berechnet. Methodik: Ein 12 kg Ferkel (8 Wochen) wurde nach i.v. Injektion von [18F]Flubatine (185.4 MBq) bis zu 4,5 h p.i. in einem PET/CT (SIEMENS Biograph 16) gemessen und die List-Mode Daten nach Standardkorrekturen rekonstruiert. Unter Nutzung der PET bzw. CT Daten und der Software ROVER (ABX, Radeberg) wurden 18 Organe vorwiegend manuell segmentiert und als DICOM Structure Set exportiert. Mit der Software OEDIPE [1] erfolgte die Zuordnung der Gewebeeigenschaften der segmentierten Organe nach ICRU [2]. Anschließend erfolgt die Simulation in MCNPX (v.2.6.0) mit 20 Millionen Events als Abbruchkriterium. Ergebnisse: Mit OEDIPE gelingt unter Verwendung des Ergebnisses der MC-Simulation die Erzeugung der SAFs für ein VP des Ferkels. Für 28 Radionuklide wurden SAFs (mGy/MBq*s) für Gehirn, Leber, Gallenblase, Nieren, Dünn- und Dickdarm, Lunge, Herz

Ziel: Bei der Translation neuartiger Radiotracer in die klinische Phase ist eine Abschätzung der Strahlenexposition vor Erstanwendung am Menschen notwendig. Hierbei werden die Organdosen (OD) sowie die effektive Dosis (ED) am Tiermodell abgeschätzt, welche nach i.v. Injektion eines Radiotracers entstehen. Erstmalig wurde Kleintier-PET/MRT zur rein bildgebungsbasierten Inkorporationsdosimetrie mit CD-1 Mäusen eingesetzt. Um den Einfluss von Speziesunterschieden zu untersuchen wurden PET/CT-Studien an Ferkeln durchgeführt und die Ergebnisse mit am Menschen erhobenen Ergebnissen (PET/CT) verglichen. Methodik: Nach i.v. Injektion von (-)- oder (+)-[18F]Flubatine (a, b) bzw. (S)- oder (R)-[18F]Fluspidine (c,d) wurden (i) In-vivo-PET/MRT- (MEDISO nanoScan, Budapest) und PET/CT-Scans (SIEMENS Biograph 16) bis zu 7 h p.i. durchgeführt, die List-Mode Daten unter Nutzung der Standardkorrekturen rekonstruiert und die Organaktivitäten (OA) mit ROVER (ABX, Radeberg) bestimmt; (ii) (a, c, d) Ex-vivo-Organentnahme an Mäusen und Messung der OA in einem Gammacounter durchgeführt (Goldstandard). Nach Extrapolation der Tierdaten auf menschliche Verhältnisse, wurden die OD und die ED mit OLINDA für 3 Spezies berechnet. Ergebnisse: Die Dosimetrie für a/b ergab eine ED (µSv/MBq) von 12,5/12,1 (30 Mäuse), 13,4/14,3 (8 Ferkel), 22,3/23,0 (n=6 Menschen) und für (c/d) 12,9/14,0 (6 Mäuse), 21,0/n.a. (4 Menschen). Während a und b eine vergleichbare Biokinetik sowie ED zeigen, ist die ED von c und d signifikant (p=0,025) verschieden basierend auf Enantiomeren Unterschieden. Weiterhin zeigt sich eine Unterschätzung der ED erhoben mit Tierdaten im Vergleich zum Menschen von 38% (Ferkel) bis 47% (Mäuse). Schlussfolgerung: Die Strahlenexposition nach i.v. Applikation von a,b,c,d liegt im Bereich der durch andere F-18-markierter Radiotracer. Die Abschätzung der ED unter Nutzung von Tiermodellen mit Hilfe eines Kleintier-PET/MRT ist unter Berücksichtigung der genannten Limitationen möglich und liefer

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we

© 2018 Elsevier B.V. Through litter decomposition enormous amounts of carbon is emitted to the atmosphere. Numerous large-scale decomposition experiments have been conducted focusing on this fundamental soil process in order to understand the controls on the terrestrial carbon transfer to the atmosphere. However, previous studies were mostly based on site-specific litter and methodologies, adding major uncertainty to syntheses, comparisons and meta-analyses across different experiments and sites. In the TeaComposition initiative, the potential litter decomposition is investigated by using standardized substrates (Rooibos and Green tea) for comparison of litter mass loss at 336 sites (ranging from −9 to +26 °C MAT and from 60 to 3113 mm MAP) across different ecosystems. In this study we tested the effect of climate (temperature and moisture), litter type and land-use on early stage decomposition (3 months) across nine biomes. We show that litter quality was the predominant controlling factor in early stage litter decomposition, which explained about 65% of the variability in litter decomposition at a global scale. The effect of climate, on the other hand, was not litter specific and explained <0.5% of the variation for Green tea and 5% for Rooibos tea, and was of significance only under unfavorable decomposition conditions (i.e. xeric versus mesic environments). When the data were aggregated at the biome scale, climate played a significant role on decomposition of both litter types (explaining 64% of the variation for Green tea and 72% for Rooibos tea). No significant effect of land-use on early stage litter decomposition was noted within the temperate biome. Our results indicate that multiple drivers are affecting early stage litter mass loss with litter quality being dominant. In order to be able to quantify the relative importance of the different drivers over time, long-term studies combined with experimental trials are needed.

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we

Introduction (+)-[18F]Flubatine ((+)[18F]NCFHEB), the enantiomer of the recently introduced radioligand for quantificati(-)-[18F]Flubatine, was investigated in a clinical trial with patients suffering from Alzheimer’s disease compared to healthy controls. In order to be able to apply full kinetic modelling biological parameters such as plasma protein binding, amount of parent compound over time and distribution between cellular and noncellular blood components, were determined. In addition the kinetics of the tracer distribution between plasma and whole blood was assessed. Methods Plasma protein binding was evaluated in vitro by means of ultracentrifugation using a blood sample from each subject prior to injection. The amount of unchanged tracer over time was determined at 11 time points ranging from 3 to 270 min p.i. by radio-HPLC analysis of protein free plasma obtained by centrifugation as described previously. The distribution of radioactivity between cellular and non-cellular blood components was determined at 11 time points p.i. after separation of the blood components by centrifugation. Results/Discussion Plasma protein binding of (-)-[18F]Flubatine was found to be 0.140.02 (meansd) without significant difference between AD and HC groups. Metabolic degradation of (+)-[18F]Flubatine was very low: the amount of parent compound was found to be 100 and 972 % at 90 and 270 min p.i., respectively. The activity distribution between plasma and whole blood was found to be 0.820.05 and did not change with time. Kinetics for the distribution of the tracer between plasma and whole blood was determined over a time period of 1.5 h and equilibrium was found to be reached instantaneously. Conclusions Biological parameters such as plasma protein binding, metabolism and tracer/activity distribution between plasma and whole blood were investigated within a clinical trial using (+)-[1842 subtype of nAChRs. From the biological data obtained within this study we, conclude that

Introduction (+)-[18F]Flubatine ((+)[18F]NCFHEB), the enantiomer of the recently introduced radioligand for quantificati(-)-[18F]Flubatine, was investigated in a clinical trial with patients suffering from Alzheimer’s disease compared to healthy controls. In order to be able to apply full kinetic modelling biological parameters such as plasma protein binding, amount of parent compound over time and distribution between cellular and noncellular blood components, were determined. In addition the kinetics of the tracer distribution between plasma and whole blood was assessed. Methods Plasma protein binding was evaluated in vitro by means of ultracentrifugation using a blood sample from each subject prior to injection. The amount of unchanged tracer over time was determined at 11 time points ranging from 3 to 270 min p.i. by radio-HPLC analysis of protein free plasma obtained by centrifugation as described previously. The distribution of radioactivity between cellular and non-cellular blood components was determined at 11 time points p.i. after separation of the blood components by centrifugation. Results/Discussion Plasma protein binding of (-)-[18F]Flubatine was found to be 0.140.02 (meansd) without significant difference between AD and HC groups. Metabolic degradation of (+)-[18F]Flubatine was very low: the amount of parent compound was found to be 100 and 972 % at 90 and 270 min p.i., respectively. The activity distribution between plasma and whole blood was found to be 0.820.05 and did not change with time. Kinetics for the distribution of the tracer between plasma and whole blood was determined over a time period of 1.5 h and equilibrium was found to be reached instantaneously. Conclusions Biological parameters such as plasma protein binding, metabolism and tracer/activity distribution between plasma and whole blood were investigated within a clinical trial using (+)-[1842 subtype of nAChRs. From the biological data obtained within this study we, conclude that

Objectives: (S)-(-)-[18F]fluspidine has been pre-clinically proven to be a distinctive radioligand for imaging 1-receptors with PET [1]. In this study, the biokinetics was studied first in man. To assess the radiation risk, the biodistribution, organ doses (OD) and the effective dose (ED) were determined. Methods: Whole body dosimetry was performed in 4 healthy volunteers (2m, 2f; age: 22.5±2.7y weight: 62.5±8.4.5kg). They were sequentially PET/CT-imaged up to 7h post i.v. injection of 264±17 MBq, 8 bed positions (BP) per frame, 1.5 to 6 min/BP, followed by CT-attenuation correction and iterative reconstruction. All micturated urine was collected up to 7 hours post injection. Urine was weighed and samples measured for radioactivity concentration [Bq/ccm] in a well counter. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/organ). The ODs were calculated using the stylized adult male model as implemented in OLINDA v1. The ED was calculated using tissue weighting factors as published in ICRP60 and 103. Results: The highest OD [µSv/MBq] was received by the liver (76.0±17.7), the gall bladder wall (60.7±10.6) and the small intestine (56.9±10.6). The highest contribution to the ED [µSv/MBq] was by the stomach wall (3.8±0.4), the lungs (3.4±0.3) and the liver (3.0±0.4). The conversion factor [µSv/MBq] to estimate the ED to humans is 22.1±1.3 (ICRP60) and 21.0±1.3 (ICRP103), respectively. Conclusions: The effective dose was calculated to be 6.3 mSv/300MBq. This is in the order of magnitude as for other 18F-labeled PET-compounds. The results provide a rationale for further clinical study phases and the development of this tracer as a clinical tool for PET imaging 1-receptors. References: [1] Brust P, Deuther-Conrad W, Becker G, Patt M, Donat CK, Stittsworth S, Fischer S, Hiller A, Wenzel B, Dukic-Stefanovic S, Hesse S, Steinbach J, Wunsch B, Lever SZ, and Sabri O (2014) Distinctive in vivo kinetics of th

Objectives: (S)-(-)-[18F]fluspidine has been pre-clinically proven to be a distinctive radioligand for imaging 1-receptors with PET [1]. In this study, the biokinetics was studied first in man. To assess the radiation risk, the biodistribution, organ doses (OD) and the effective dose (ED) were determined. Methods: Whole body dosimetry was performed in 4 healthy volunteers (2m, 2f; age: 22.5±2.7y weight: 62.5±8.4.5kg). They were sequentially PET/CT-imaged up to 7h post i.v. injection of 264±17 MBq, 8 bed positions (BP) per frame, 1.5 to 6 min/BP, followed by CT-attenuation correction and iterative reconstruction. All micturated urine was collected up to 7 hours post injection. Urine was weighed and samples measured for radioactivity concentration [Bq/ccm] in a well counter. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/organ). The ODs were calculated using the stylized adult male model as implemented in OLINDA v1. The ED was calculated using tissue weighting factors as published in ICRP60 and 103. Results: The highest OD [µSv/MBq] was received by the liver (76.0±17.7), the gall bladder wall (60.7±10.6) and the small intestine (56.9±10.6). The highest contribution to the ED [µSv/MBq] was by the stomach wall (3.8±0.4), the lungs (3.4±0.3) and the liver (3.0±0.4). The conversion factor [µSv/MBq] to estimate the ED to humans is 22.1±1.3 (ICRP60) and 21.0±1.3 (ICRP103), respectively. Conclusions: The effective dose was calculated to be 6.3 mSv/300MBq. This is in the order of magnitude as for other 18F-labeled PET-compounds. The results provide a rationale for further clinical study phases and the development of this tracer as a clinical tool for PET imaging 1-receptors. References: [1] Brust P, Deuther-Conrad W, Becker G, Patt M, Donat CK, Stittsworth S, Fischer S, Hiller A, Wenzel B, Dukic-Stefanovic S, Hesse S, Steinbach J, Wunsch B, Lever SZ, and Sabri O (2014) Distinctive in vivo kinetics of th

Objectives: (S)-(-)-[18F]fluspidine has been pre-clinically proven to be a distinctive radioligand for imaging 1-receptors with PET [1]. In this study, the biokinetics was studied first in man. To assess the radiation risk, the biodistribution, organ doses (OD) and the effective dose (ED) were determined. Methods: Whole body dosimetry was performed in 4 healthy volunteers (2m, 2f; age: 22.5±2.7y weight: 62.5±8.4.5kg). They were sequentially PET/CT-imaged up to 7h post i.v. injection of 264±17 MBq, 8 bed positions (BP) per frame, 1.5 to 6 min/BP, followed by CT-attenuation correction and iterative reconstruction. All micturated urine was collected up to 7 hours post injection. Urine was weighed and samples measured for radioactivity concentration [Bq/ccm] in a well counter. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/organ). The ODs were calculated using the stylized adult male model as implemented in OLINDA v1. The ED was calculated using tissue weighting factors as published in ICRP60 and 103. Results: The highest OD [µSv/MBq] was received by the liver (76.0±17.7), the gall bladder wall (60.7±10.6) and the small intestine (56.9±10.6). The highest contribution to the ED [µSv/MBq] was by the stomach wall (3.8±0.4), the lungs (3.4±0.3) and the liver (3.0±0.4). The conversion factor [µSv/MBq] to estimate the ED to humans is 22.1±1.3 (ICRP60) and 21.0±1.3 (ICRP103), respectively. Conclusions: The effective dose was calculated to be 6.3 mSv/300MBq. This is in the order of magnitude as for other 18F-labeled PET-compounds. The results provide a rationale for further clinical study phases and the development of this tracer as a clinical tool for PET imaging 1-receptors. References: [1] Brust P, Deuther-Conrad W, Becker G, Patt M, Donat CK, Stittsworth S, Fischer S, Hiller A, Wenzel B, Dukic-Stefanovic S, Hesse S, Steinbach J, Wunsch B, Lever SZ, and Sabri O (2014) Distinctive in vivo kinetics of th

Objectives : (-)-[18F]flubatine is successfully used for neuroimaging of alpha4beta2 nicotinic acetylcholine receptors in human. In this study the biokinetic of the (+) enantiomer was studied first time into humans. To assess the radiation risk by this new radioligand the biodistribution, organ doses (OD) and the effective dose (ED) were determined in 3 healthy volunteers. The results will be compared to the preclinical (mice: PET/MR piglets: PET/CT) and clinical (PET/CT) data and to the (-) enantiomer of flubatine [1]. Methods : Whole body dosimetry was performed in 3 healthy volunteers (2 m, 1 f ; age: 58.3±5.8 y weight: 80.7±5.5 kg). The volunteers were sequentially PET-imaged up to 7h post i.v. injection of 285±13 MBq on a SIEMENS Biograph16 PET/CT-system on 9 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results : The highest OD [µSv/MBq] was received by urinary bladder (102.0 ± 29.6) and liver (53.1±29.8). The highest contribution to the ED [µSv/MBq] was by urinary bladder (4.1±1.2) and lungs (3.2±0.3). The estimated ED in humans is 23.0±1.9. Conclusions : The overall radiation risk was calculated to be 6.9 mSv/300MBq which is almost identically with the results of the (-)-enantiomer in humans (7.02 mSv/MBq). This is in the same magnitude as for other 18F labeled compounds too. Furthermore, the underestimation of the ED to humans based on preclinical data as mentioned in [1] could be verified for mice (12.1 µSv/MBq) and piglets (14.3 µSv/MBq) with this tracer too. This supports the use of animal image derived data for preclinical dose assessment to humans taking into account an underestimation of about 4

This paper summarises the proceedings and discussions at the third annual workshop held in Tubingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with "hands-on" tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: "the real work has just started".

Objectives : (-)-[18F]flubatine is successfully used for neuroimaging of alpha4beta2 nicotinic acetylcholine receptors in human. In this study the biokinetic of the (+) enantiomer was studied first time into humans. To assess the radiation risk by this new radioligand the biodistribution, organ doses (OD) and the effective dose (ED) were determined in 3 healthy volunteers. The results will be compared to the preclinical (mice: PET/MR piglets: PET/CT) and clinical (PET/CT) data and to the (-) enantiomer of flubatine [1]. Methods : Whole body dosimetry was performed in 3 healthy volunteers (2 m, 1 f ; age: 58.3±5.8 y weight: 80.7±5.5 kg). The volunteers were sequentially PET-imaged up to 7h post i.v. injection of 285±13 MBq on a SIEMENS Biograph16 PET/CT-system on 9 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results : The highest OD [µSv/MBq] was received by urinary bladder (102.0 ± 29.6) and liver (53.1±29.8). The highest contribution to the ED [µSv/MBq] was by urinary bladder (4.1±1.2) and lungs (3.2±0.3). The estimated ED in humans is 23.0±1.9. Conclusions : The overall radiation risk was calculated to be 6.9 mSv/300MBq which is almost identically with the results of the (-)-enantiomer in humans (7.02 mSv/MBq). This is in the same magnitude as for other 18F labeled compounds too. Furthermore, the underestimation of the ED to humans based on preclinical data as mentioned in [1] could be verified for mice (12.1 µSv/MBq) and piglets (14.3 µSv/MBq) with this tracer too. This supports the use of animal image derived data for preclinical dose assessment to humans taking into account an underestimation of about 4

This workshop was held a year after the initial positron emission tomography/magnetic resonance (PET/MR) workshop in Tübingen, which was recently reported in this journal. The discussions at the 2013 workshop, however, differed substantially from those of the initial workshop, attesting to the progress of combined PET/MR as an innovative imaging modality. Discussions were focused on the search for truly novel, unique clinical and research applications as well as technical issues such as reliable and accurate approaches for attenuation and scatter correction of PET emission data. The workshop provided hands-on experience with PET and MR imaging. In addition, structured and moderated open discussion sessions, including six dialogue boards and two roundtable discussions, provided input from current and future PET/MR imaging users. This summary provides a snapshot of the current achievements and challenges for PET/MR.

Software-implemented fault injection (SWIFI) is an established experimental technique to evaluate the robustness of software systems. While a large number of SWIFI frameworks exist, virtually all are based on a single-fault assumption, i.e., interactions of simultaneously occurring independent faults are not investigated. As software systems containing more than a single fault often are the norm than an exception [1] and current safety standards require the consideration of 'multi-point faults' [2], the validity of this single-fault assumption is at question for contemporary software systems. To address the issue and support simultaneous SWIFI (simFI), we analyze how independent faults can manifest in a generic software composition model and extend an existing SWIFI tool to support some characteristic simultaneous fault types. We implement three simultaneous fault models and demonstrate their utility in evaluating the robustness of the Windows CE kernel. Our findings indicate that simultaneous fault injections prove highly efficient in triggering robustness vulnerabilities. © 2013 IEEE.

Ziel: (+)-[F-18]flubatine is a new tracer for neuroimaging of alpha4beta2 nAChRs with PET. To assess the radiation risk after intravenous application of the radioligand, the biodistribution, organ doses (OD) and the effective dose (ED) were assessed in pigs and compared to results based on data using the stereoisomere (-)-[F-18]flubatine. Methodik: Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg) The animals were narcotized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq (+)-[F-18]flubatine on a SIEMENS Biograph16 PET/CT-system with 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Ergebnisse: The highest OD was received by the urinary bladder (71.7±26.3µSv/MBq), the kidneys (45.1±6.5 µSv/MBq) and the brain (32.3±3.24µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.9±1.1 µSv/MBq), the lungs (1.7±0.02µSv/MBq) and the red marrow (1.4±0.1µSv/MBq). According to this data, the ED to humans is 14.3±0.3 µSv/MBq. Schlussfolgerungen: The effective dose upon i.v. application of about 300 MBq (+)-[F-18]flubatine to humans would be 7.1 mSv, taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%. This is well within the range of what is caused by other F18-labeled compounds to humans. This risk assessment encourages to transfer (+)-[F-18]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain.

Objectives : (+)-[18F]flubatine is the mirror image isomer of (-)-[18F]flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs in human. To assess the radiation risk by this new radioligand, biodistribution, organ doses (OD) and the effective dose (ED) were determined in piglets. Methods : Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg). The animals were anesthetized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq on a SIEMENS Biograph16 PET/CT-system on 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results : The highest OD [µSv/MBq] was received by urinary bladder (71.7±26.3) and kidneys (45.1±6.5). The highest contribution to ED [µSv/MBq] was by urinary bladder (2.9±1.1) and lungs (1.7±0.02). The estimated ED to humans is 14.3±0.3. Conclusions : Considering 40% underestimation of the ED to humans by preclinical dosimetry [1], the expected ED to humans after 300MBq i.v. is 7.2 mSv, which is about the ED by (-)-[18F]flubatine (6.8 mSv/300MBq) and well within the range of what other F-18-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[18F]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain. [1] Sattler B, …, Sabri O. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results. J. Nucl. Med. 2012; 53(suppl): 1503. Research Support: The trial is partly co-funded by Strahlenschutzseminar

Objectives : (+)-[18F]flubatine is the mirror image isomer of (-)-[18F]flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs in human. To assess the radiation risk by this new radioligand, biodistribution, organ doses (OD) and the effective dose (ED) were determined in piglets. Methods : Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg). The animals were anesthetized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq on a SIEMENS Biograph16 PET/CT-system on 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results : The highest OD [µSv/MBq] was received by urinary bladder (71.7±26.3) and kidneys (45.1±6.5). The highest contribution to ED [µSv/MBq] was by urinary bladder (2.9±1.1) and lungs (1.7±0.02). The estimated ED to humans is 14.3±0.3. Conclusions : Considering 40% underestimation of the ED to humans by preclinical dosimetry [1], the expected ED to humans after 300MBq i.v. is 7.2 mSv, which is about the ED by (-)-[18F]flubatine (6.8 mSv/300MBq) and well within the range of what other F-18-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[18F]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain. [1] Sattler B, …, Sabri O. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results. J. Nucl. Med. 2012; 53(suppl): 1503. Research Support: The trial is partly co-funded by Strahlenschutzseminar

Ziel: (+)-[F-18]flubatine is a new tracer for neuroimaging of alpha4beta2 nAChRs with PET. To assess the radiation risk after intravenous application of the radioligand, the biodistribution, organ doses (OD) and the effective dose (ED) were assessed in pigs and compared to results based on data using the stereoisomere (-)-[F-18]flubatine. Methodik: Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg) The animals were narcotized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq (+)-[F-18]flubatine on a SIEMENS Biograph16 PET/CT-system with 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Ergebnisse: The highest OD was received by the urinary bladder (71.7±26.3µSv/MBq), the kidneys (45.1±6.5 µSv/MBq) and the brain (32.3±3.24µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.9±1.1 µSv/MBq), the lungs (1.7±0.02µSv/MBq) and the red marrow (1.4±0.1µSv/MBq). According to this data, the ED to humans is 14.3±0.3 µSv/MBq. Schlussfolgerungen: The effective dose upon i.v. application of about 300 MBq (+)-[F-18]flubatine to humans would be 7.1 mSv, taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%. This is well within the range of what is caused by other F18-labeled compounds to humans. This risk assessment encourages to transfer (+)-[F-18]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain.

Software-implemented fault injection (SWIFI) is an established experimental technique to evaluate the robustness of software systems. While a large number of SWIFI frameworks exist, virtually all are based on a single-fault assumption, i.e., interactions of simultaneously occurring independent faults are not investigated. As software systems containing more than a single fault often are the norm than an exception [1] and current safety standards require the consideration of 'multi-point faults' [2], the validity of this single-fault assumption is at question for contemporary software systems. To address the issue and support simultaneous SWIFI (simFI), we analyze how independent faults can manifest in a generic software composition model and extend an existing SWIFI tool to support some characteristic simultaneous fault types. We implement three simultaneous fault models and demonstrate their utility in evaluating the robustness of the Windows CE kernel. Our findings indicate that simultaneous fault injections prove highly efficient in triggering robustness vulnerabilities. © 2013 IEEE.

Objectives : (+)-[18F]flubatine is the mirror image isomer of (-)-[18F]flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs in human. To assess the radiation risk by this new radioligand, biodistribution, organ doses (OD) and the effective dose (ED) were determined in piglets. Methods : Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg). The animals were anesthetized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq on a SIEMENS Biograph16 PET/CT-system on 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results : The highest OD [µSv/MBq] was received by urinary bladder (71.7±26.3) and kidneys (45.1±6.5). The highest contribution to ED [µSv/MBq] was by urinary bladder (2.9±1.1) and lungs (1.7±0.02). The estimated ED to humans is 14.3±0.3. Conclusions : Considering 40% underestimation of the ED to humans by preclinical dosimetry [1], the expected ED to humans after 300MBq i.v. is 7.2 mSv, which is about the ED by (-)-[18F]flubatine (6.8 mSv/300MBq) and well within the range of what other F-18-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[18F]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain. [1] Sattler B, …, Sabri O. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results. J. Nucl. Med. 2012; 53(suppl): 1503. Research Support: The trial is partly co-funded by Strahlenschutzseminar

Objectives : (+)-[18F]flubatine is the mirror image isomer of (-)-[18F]flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs in human. To assess the radiation risk by this new radioligand, biodistribution, organ doses (OD) and the effective dose (ED) were determined in piglets. Methods : Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg). The animals were anesthetized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq on a SIEMENS Biograph16 PET/CT-system on 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results : The highest OD [µSv/MBq] was received by urinary bladder (71.7±26.3) and kidneys (45.1±6.5). The highest contribution to ED [µSv/MBq] was by urinary bladder (2.9±1.1) and lungs (1.7±0.02). The estimated ED to humans is 14.3±0.3. Conclusions : Considering 40% underestimation of the ED to humans by preclinical dosimetry [1], the expected ED to humans after 300MBq i.v. is 7.2 mSv, which is about the ED by (-)-[18F]flubatine (6.8 mSv/300MBq) and well within the range of what other F-18-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[18F]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain. [1] Sattler B, …, Sabri O. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results. J. Nucl. Med. 2012; 53(suppl): 1503. Research Support: The trial is partly co-funded by Strahlenschutzseminar

Objectives : (+)-[18F]flubatine is the mirror image isomer of (-)-[18F]flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs in human. To assess the radiation risk by this new radioligand, biodistribution, organ doses (OD) and the effective dose (ED) were determined in piglets. Methods : Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg). The animals were anesthetized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq on a SIEMENS Biograph16 PET/CT-system on 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results : The highest OD [µSv/MBq] was received by urinary bladder (71.7±26.3) and kidneys (45.1±6.5). The highest contribution to ED [µSv/MBq] was by urinary bladder (2.9±1.1) and lungs (1.7±0.02). The estimated ED to humans is 14.3±0.3. Conclusions : Considering 40% underestimation of the ED to humans by preclinical dosimetry [1], the expected ED to humans after 300MBq i.v. is 7.2 mSv, which is about the ED by (-)-[18F]flubatine (6.8 mSv/300MBq) and well within the range of what other F-18-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[18F]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain. [1] Sattler B, …, Sabri O. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results. J. Nucl. Med. 2012; 53(suppl): 1503. Research Support: The trial is partly co-funded by Strahlenschutzseminar

Ziel: (+)-[F-18]flubatine is a new tracer for neuroimaging of alpha4beta2 nAChRs with PET. To assess the radiation risk after intravenous application of the radioligand, the biodistribution, organ doses (OD) and the effective dose (ED) were assessed in pigs and compared to results based on data using the stereoisomere (-)-[F-18]flubatine. Methodik: Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg) The animals were narcotized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq (+)-[F-18]flubatine on a SIEMENS Biograph16 PET/CT-system with 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Ergebnisse: The highest OD was received by the urinary bladder (71.7±26.3µSv/MBq), the kidneys (45.1±6.5 µSv/MBq) and the brain (32.3±3.24µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.9±1.1 µSv/MBq), the lungs (1.7±0.02µSv/MBq) and the red marrow (1.4±0.1µSv/MBq). According to this data, the ED to humans is 14.3±0.3 µSv/MBq. Schlussfolgerungen: The effective dose upon i.v. application of about 300 MBq (+)-[F-18]flubatine to humans would be 7.1 mSv, taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%. This is well within the range of what is caused by other F18-labeled compounds to humans. This risk assessment encourages to transfer (+)-[F-18]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain.

Purpose: To provide a guideline curriculum covering theoretical and practical aspects of education and training for Medical Physicists in Nuclear Medicine within Europe. Material and methods: National training programmes of Medical Physics, Radiation Physics and Nuclear Medicine physics from a range of European countries and from North America were reviewed and elements of best practice identified. An independent panel of experts was used to achieve consensus regarding the content of the curriculum. Results: Guidelines have been developed for the specialist theoretical knowledge and practical experience required to practice as a Medical Physicist in Nuclear Medicine in Europe. It is assumed that the precondition for the beginning of the training is a good initial degree in Medical Physics at master level (or equivalent). The Learning Outcomes are categorised using the Knowledge, Skill and Competence approach along the lines recommended by the European Qualifications Framework. The minimum level expected in each topic in the theoretical knowledge and practical experience sections is intended to bring trainees up to the requirements expected of a Medical Physicist entering the field of Nuclear Medicine. Conclusions: This new joint EANM/EFOMP European guideline curriculum is a further step to harmonise specialist training of Medical Physicists in Nuclear Medicine within Europe. It provides a common framework for national Medical Physics societies to develop or benchmark their own curricula. The responsibility for the implementation and accreditation of these standards and guidelines resides within national training and regulatory bodies.

Item does not contain fulltext, This work addresses the clinical adoption of FDG-PET/CT for image-guided radiation therapy planning (RTP). As such, important technical and methodological aspects of PET/CT-based RTP are reviewed and practical recommendations are given for routine patient management and clinical studies. First, recent developments in PET/CT hardware that are relevant to RTP are reviewed in the context of quality control and system calibration procedures that are mandatory for a reproducible adoption of PET/CT in RTP. Second, recommendations are provided on image acquisition and reconstruction to support the standardization of imaging protocols. A major prerequisite for routine RTP is a complete and secure data transfer to the actual planning system. Third, state-of-the-art tools for image fusion and co-registration are discussed briefly in the context of PET/CT imaging pre- and post-RTP. This includes a brief review of state-of-the-art image contouring algorithms relevant to PET/CT-guided RTP. Finally, practical aspects of clinical workflow and patient management, such as patient setup and requirements for staff training are emphasized. PET/CT-guided RTP mandates attention to logistical aspects, patient set-up and acquisition parameters as well as an in-depth appreciation of quality control and protocol standardization. Conclusion: Upon fulfilling the requirements to perform PET/CT for RTP, a new dimension of molecular imaging can be added to traditional morphological imaging. As a consequence, PET/CT imaging will support improved RTP and better patient care. This document serves as a guidance on practical and clinically validated instructions that are deemed useful to the staff involved in PET/CT-guided RTP.