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This study describes the synthesis, radiofluorination and purification of an anionic amphiphilic teroligomer developed as stabilizer for siRNA-loaded calcium phosphate nanoparticles (CaP-NP). As the stabilizing amphiphile accumulates on nanoparticle surfaces, the fluorine-18 labeled polymer should enable to track the distribution of the CaP-NP in brain tumors after ap-plication by convection-enhanced delivery. At first, an unmodified teroligomer was synthesized with a number average molecular weight of 4550 ± 20 Da by free radical polymerization of a de-fined composition of methoxy-PEG-monomethacrylate, tetradecyl acrylate and maleic anhy-dride. Subsequent derivatization of anhydrides with azido-TEG-amine provided an azido func-tionalized polymer precursor (o14PEGMA-1) for radiofluorination. The 18F-labeling was accom-plished by copper-catalyzed cycloaddition of o14PEGMA-1 with the diethylene glycol - alkyne substituted heteroaromatic prosthetic group [18F]2 which was synthesized with a radiochemical yield (RCY) of about 38% within 60 min using a radiosynthesis module. The 18F-labeled polymer [18F]fluoro-o14PEGMA-2 was obtained after a short reaction time of 2-3 min by using CuSO4/sodium ascorbate at 90 °C. Purification was performed by solid-phase extraction on an anion-exchange cartridge followed by size-exclusion chromatography to obtain [18F]fluoro-o14PEGMA-2 with a high radiochemical purity and an RCY of about 15%.

PURPOSE This paper presents the results of the first joint survey on the use of SPECT and PET myocardial perfusion imaging (MPI) and cardiac amyloidosis imaging in Austria, Germany, and Switzerland of the year 2021. METHODS A questionnaire was sent in 2022 to centres practicing nuclear medicine. RESULTS Data from 14 Austrian (10,710 SPECT), 218 German (133,047 SPECT), and 16 Swiss centres (11,601 MPI (6,879 SPECT, 4722 PET)) were analysed. In Austria and Germany, the PET MPI numbers were close to zero and not considered. Official MPS numbers from 2015 to 2021 from Austria and Germany revealed a decline in Austria by about 40% in the pandemic years 2020 to 2021, but an increase in Germany by 9%. Ambulatory care cardiologists represented the major referral group (56-71%). Mostly, stress tests were performed pharmacologically (58-92%). Contrary to Germany, a 1-day protocol was predominant (58-97%) in Austria and Switzerland. The leading camera systems were SPECT-CT in Austria and Switzerland (57-79%) and multi-head systems in Germany (58%). Switzerland had the highest proportion of SPECT MPI with attenuation correction (84%), followed by Austria (43%), and Germany (33%). Electrocardiogram-gated SPECT MPI showed an overall high penetration of 87-99%. Scoring was most frequently applied in Germany (72%), followed by Austria (64%), and Switzerland (60%). Related to the population, the number of cardiac amyloidosis imaging was highest in Austria, followed by Switzerland and Germany. CONCLUSIONS This first joint survey of 2021 shows considerable differences among the countries. The Swiss situation is outstanding due to the wide use of PET MPI. In terms of camera equipment, Switzerland is also leading, followed by Austria and Germany. Despite the differences in procedural issues, the results reveal an overall high standard of MPI imaging.

PURPOSE: To assess whether a radiomics and machine learning (ML) model combining quantitative parameters and radiomics features extracted from simultaneous multiparametric 18F-FDG PET/MRI can discriminate between benign and malignant breast lesions. METHODS: A population of 102 patients with 120 breast lesions (101 malignant and 19 benign) detected on ultrasound and/or mammography was prospectively enrolled. All patients underwent hybrid 18F-FDG PET/MRI for diagnostic purposes. Quantitative parameters were extracted from DCE (MTT, VD, PF), DW (mean ADC of breast lesions and contralateral breast parenchyma), PET (SUVmax, SUVmean, and SUVminimum of breast lesions, as well as SUVmean of the contralateral breast parenchyma), and T2-weighted images. Radiomics features were extracted from DCE, T2-weighted, ADC, and PET images. Different diagnostic models were developed using a fine Gaussian support vector machine algorithm which explored different combinations of quantitative parameters and radiomics features to obtain the highest accuracy in discriminating between benign and malignant breast lesions using fivefold cross-validation. The performance of the best radiomics and ML model was compared with that of expert reader review using McNemar's test. RESULTS: Eight radiomics models were developed. The integrated model combining MTT and ADC with radiomics features extracted from PET and ADC images obtained the highest accuracy for breast cancer diagnosis (AUC 0.983), although its accuracy was not significantly higher than that of expert reader review (AUC 0.868) (p = 0.508). CONCLUSION: A radiomics and ML model combining quantitative parameters and radiomics features extracted from simultaneous multiparametric 18F-FDG PET/MRI images can accurately discriminate between benign and malignant breast lesions.

PURPOSE: To investigate whether a machine learning (ML)-based radiomics model applied to 18F-FDG PET/MRI is effective in molecular subtyping of breast cancer (BC) and specifically in discriminating triple negative (TN) from other molecular subtypes of BC. METHODS: Eighty-six patients with 98 BC lesions (Luminal A = 10, Luminal B = 51, HER2+ = 12, TN = 25) were included and underwent simultaneous 18F-FDG PET/MRI of the breast. A 3D segmentation of BC lesion was performed on T2w, DCE, DWI and PET images. Quantitative diffusion and metabolic parameters were calculated and radiomics features extracted. Data were selected using the LASSO regression and used by a fine gaussian support vector machine (SVM) classifier with a 5-fold cross validation for identification of TNBC lesions. RESULTS: Eight radiomics models were built based on different combinations of quantitative parameters and/or radiomic features. The best performance (AUROC 0.887, accuracy 82.8%, sensitivity 79.7%, specificity 86%, PPV 85.3%, NPV 80.8%) was found for the model combining first order, neighborhood gray level dependence matrix and size zone matrix-based radiomics features extracted from ADC and PET images. CONCLUSION: A ML-based radiomics model applied to 18F-FDG PET/MRI is able to non-invasively discriminate TNBC lesions from other BC molecular subtypes with high accuracy. In a future perspective, a "virtual biopsy" might be performed with radiomics signatures.

Convection-enhanced delivery (CED) has been introduced as a concept in cancer treatment to generate high local concentrations of anticancer therapeutics and overcome the limited diffusional distribution, e.g., in the brain. RNA interference provides interesting therapeutic options to fight cancer cells but requires nanoparticulate (NP) carriers with a size below 100 nm as well as a low zeta potential for CED application. In this study, we investigated calcium phosphate NPs (CaP-NPs) as siRNA carriers for CED application. Since CaP-NPs tend to aggregate, we introduced a new terpolymer (o14PEGMA(1:1:2.5) NH3) for stabilization of CaP-NPs intended for delivery of siRNA to brain cancer cells. This small terpolymer provides PEG chains for steric stabilization, and a fat alcohol to improve interfacial activity, as well as maleic anhydrides that allow for both labeling and high affinity to Ca(II) in the hydrolyzed state. In a systematic approach, we varied the Ca/P ratio as well as the terpolymer concentration and successfully stabilized NPs with the desired properties. Labeling of the terpolymer with the fluorescent dye Cy5 revealed the terpolymer’s high affinity to CaP. Importantly, we also determined a high efficiency of siRNA binding to the NPs that caused very effective survivin siRNA silencing in F98 rat brain cancer cells. Cytotoxicity investigations with a standard cell line resulted in minor and transient effects; no adverse effects were observed in organotypic brain slice cultures. However, more specific cytotoxicity investigations are required. This study provides a systematic and mechanistic analysis characterizing the effects of the first oligomer of a new class of stabilizers for siRNA-loaded CaP-NPs.

Inorganic nano drug delivery vehicles require the use of an appropriate organic stabilizer. Examples are uncharged thiol containing macromolecules or polymers for gold NPs [1] , positively charged polyethylenimines for metals [2], or carboxylate bearing polymers for cationic calcium phosphates [3].To match a variety of demands, including ion interaction, solubility, good synthetic availability, cellular uptake and endosomal escape, we present the synthesis of amphiphilic functionalizable terpolymers. Our work is based on a broad experience in the synthesis and application of free radical synthesis of maleic anhydride-containing cooligomers. [4],[5],[6] The shown terpolymers [Fig. 1] consist of tetradecylacrylate (14), methoxy-poly(ethylenglycol) methacrylate (PEG, Mn 950) and maleic anhydride (MA). The addition of filler monomers such as 4-acryloylmorpholine (AMO) or N-vinylpyrrolidone (NVP) has also been realized. Reactive anhydride moieties allowed for accessible functionalization by amide formation e.g. with Cy5 amine as fluorescent label or with the azide linker (11-azido-3,6,9-trioxaundecan-1-amine) which renders the oligomers accessible for any kind of Cu (I) catalysed azide alkyne click reaction. Figure 1: A Anhydride-containing terpolymer synthesis and B illustration of stabilization of in situ generated siRNA-loaded calcium phosphate nanoparticles. Anhydride content and intactness were determined by conductometric titration. 1H-NMR was used to quantify comonomer integration and size exclusion chromatography for molecular weight analysis. Terpolymer synthesis yields ranged between 24.1 and 51.1%, and molecular weights between 4500 and 6500 Da. MA incorporation was controlled by the reaction feed and anhydride intactness in the oligomers was higher than 60% (o14PEGMA (4/4/10)). Effects of comonomer feed on integration in the resulting purified oligomers are presented. Pristine oligomers were transferred to the respective polyanionic ammonia salt. The here pre

Inorganic nano drug delivery vehicles require the use of an appropriate organic stabilizer. Examples are uncharged thiol containing macromolecules or polymers for gold NPs [1] , positively charged polyethylenimines for metals [2], or carboxylate bearing polymers for cationic calcium phosphates [3].To match a variety of demands, including ion interaction, solubility, good synthetic availability, cellular uptake and endosomal escape, we present the synthesis of amphiphilic functionalizable terpolymers. Our work is based on a broad experience in the synthesis and application of free radical synthesis of maleic anhydride-containing cooligomers. [4],[5],[6] The shown terpolymers [Fig. 1] consist of tetradecylacrylate (14), methoxy-poly(ethylenglycol) methacrylate (PEG, Mn 950) and maleic anhydride (MA). The addition of filler monomers such as 4-acryloylmorpholine (AMO) or N-vinylpyrrolidone (NVP) has also been realized. Reactive anhydride moieties allowed for accessible functionalization by amide formation e.g. with Cy5 amine as fluorescent label or with the azide linker (11-azido-3,6,9-trioxaundecan-1-amine) which renders the oligomers accessible for any kind of Cu (I) catalysed azide alkyne click reaction. Figure 1: A Anhydride-containing terpolymer synthesis and B illustration of stabilization of in situ generated siRNA-loaded calcium phosphate nanoparticles. Anhydride content and intactness were determined by conductometric titration. 1H-NMR was used to quantify comonomer integration and size exclusion chromatography for molecular weight analysis. Terpolymer synthesis yields ranged between 24.1 and 51.1%, and molecular weights between 4500 and 6500 Da. MA incorporation was controlled by the reaction feed and anhydride intactness in the oligomers was higher than 60% (o14PEGMA (4/4/10)). Effects of comonomer feed on integration in the resulting purified oligomers are presented. Pristine oligomers were transferred to the respective polyanionic ammonia salt. The here pre

In the latest update of the European Society of Cardiology (ESC) guidelines for the management of infective endocarditis (IE), imaging is positioned at the centre of the diagnostic work-up so that an early and accurate diagnosis can be reached. Besides echocardiography, contrast-enhanced CT (ce-CT), radiolabelled leucocyte (white blood cell, WBC) SPECT/CT and [18F]FDG PET/CT are included as diagnostic tools in the diagnostic flow chart for IE. Following the clinical guidelines that provided a straightforward message on the role of multimodality imaging, we believe that it is highly relevant to produce specific recommendations on nuclear multimodality imaging in IE and cardiac implantable electronic device infections. In these procedural recommendations we therefore describe in detail the technical and practical aspects of WBC SPECT/CT and [18F]FDG PET/CT, including ce-CT acquisition protocols. We also discuss the advantages and limitations of each procedure, specific pitfalls when interpreting images, and the most important results from the literature, and also provide recommendations on the appropriate use of multimodality imaging.

Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During the meeting, cross-speciality participants assessed critical aspects of non-invasive, quantitative biomarker development in view of the need to expand our understanding of disease mechanisms and the definition of appropriate strategies both for molecular diagnostics and personalised therapies. More specifically, panelists addressed the main topics, including the current status of disease characterisation by means of non-invasive imaging, histopathology and liquid biopsies as well as strategies of gaining new understanding of disease formation, modulation and plasticity to large-scale molecular imaging as well as integrative multi-platform approaches. Highlights of the 2018 meeting included dedicated sessions on non-invasive disease characterisation, development of disease and therapeutic tailored biomarkers, standardisation and quality measures in biospecimens, new therapeutic approaches and socio-economic challenges of biomarker developments. The scientific programme was accompanied by a roundtable discussion on identification and implementation of sustainable strategies to address the educational needs in the rapidly evolving field of molecular diagnostics. The central theme that emanated from the 2nd Donau Symposium was the importance of the conceptualisation and implementation of a convergent approach towards a disease characterisation beyond lesion-counting "lumpology" for a cost-effective and patient-centric diagnosis, therapy planning, guidance and monitoring. This involves a judicious choice of diagnostic means, the adoption of clinical decision support systems and, above all, a new way of communication involving all stakeholders across modalities and specialities. Moreover, complex diseases require a comprehensive diagnosis by converging parameters from different disciplines, which will finally yi

The authors P. Orellana and N. El-Haj were inadvertently deleted in the original paper.

Contains fulltext : 215527.pdf (publisher's version ) (Open Access), Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TalphaT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TalphaT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TalphaT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TalphaT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TalphaTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TalphaTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TalphaT trial development suggest that TalphaT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TalphaT in prostate cancer treatment.

Contains fulltext : 215527.pdf (publisher's version ) (Open Access), Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TalphaT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TalphaT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TalphaT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TalphaT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TalphaTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TalphaTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TalphaT trial development suggest that TalphaT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TalphaT in prostate cancer treatment.

Contains fulltext : 215527.pdf (publisher's version ) (Open Access), Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TalphaT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TalphaT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TalphaT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TalphaT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TalphaTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TalphaTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TalphaT trial development suggest that TalphaT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TalphaT in prostate cancer treatment.

Contains fulltext : 215527.pdf (publisher's version ) (Open Access), Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TalphaT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TalphaT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TalphaT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TalphaT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TalphaTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TalphaTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TalphaT trial development suggest that TalphaT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TalphaT in prostate cancer treatment.

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

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

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

Positron emission tomography (PET) and magnetic resonance imaging (MRI) have both been used for decades in cardiovascular imaging. Since 2010, hybrid PET/MRI using sequential and integrated scanner platforms has been available, with hybrid cardiac PET/MR imaging protocols increasingly incorporated into clinical workflows. Given the range of complementary information provided by each method, the use of hybrid PET/MRI may be justified and beneficial in particular clinical settings for the evaluation of different disease entities. In the present joint position statement, we critically review the role and value of integrated PET/MRI in cardiovascular imaging, provide a technical overview of cardiac PET/MRI and practical advice related to the cardiac PET/MRI workflow, identify cardiovascular applications that can potentially benefit from hybrid PET/MRI, and describe the needs for future development and research. In order to encourage its wide dissemination, this article is freely accessible on the European Radiology and European Journal of Hybrid Imaging web sites. Key Points: • Studies and case-reports indicate that PET/MRI is a feasible and robust technology. • Promising fields of application include a variety of cardiac conditions. • Larger studies are required to demonstrate its incremental and cost-effective value. • The translation of novel radiopharmaceuticals and MR-sequences will provide exciting new opportunities.

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

Table of contentsA1 68Ga-PSMA PET/CT in staging and restaging of Prostate Cancer Patients: comparative study with 18F-Choline PET/CTW Langsteger, A Rezaee, W Loidl, HS Geinitz, F Fitz, M Steinmair, G Broinger, L Pallwien-Prettner, M BeheshtiA2 F18 Choline PET - CT: an accurate diagnostic tool for the detection of parathyroid adenoma?L Imamovic, M Beheshti, G Rendl, D Hackl, O Tsybrovsky, M Steinmair, K Emmanuel, F Moinfar, C Pirich, W LangstegerA3 [18F]Fluoro-DOPA-PET/CT in the primary diagnosis of medullary thyroid carcinomaA Bytyqi, G Karanikas, M Mayerhöfer, O Koperek, B Niederle, M HartenbachA4 Variations of clinical PET/MR operations: An international survey on the clinical utilization of PET/MRIT Beyer, K Herrmann, J CzerninA5 Standard Dixon-based attenuation correction in combined PET/MRI: Reproducibility and the possibility of Lean body mass estimationI Rausch, P Rust, MD DiFranco, M Lassen, A Stadlbauer, ME Mayerhöfer, M Hartenbach, M Hacker, T BeyerA6 High resolution digital FDG PET/MRI imaging for assessment of ACL graft viabilityK Binzel, R Magnussen, W Wei, MU Knopp, DC Flanigan, C Kaeding, MV KnoppA7 Using pre-existing hematotoxicity as predictor for severe side effects and number of treatment cycles of Xofigo therapyA Leisser, M Nejabat, M Hartenbach, G Kramer, M Krainer, M Hacker, A HaugA8 QDOSE - comprehensive software solution for internal dose assessmentWencke Lehnert, Karl Schmidt, Sharok Kimiaei, Marcus Bronzel, Andreas KlugeA9 Clinical impact of Time-of-Flight on next-generation digital PET imaging of Yttrium-90 radioactivity following liver radioembolizationCL Wright, K Binzel, J Zhang, Evan Wuthrick, Piotr Maniawski, MV KnoppA10 Snakes in patients! Lessons learned from programming active contours for automated organ segmentationM Blaickner, E Rados, A Huber, M Dulovits, H Kulkarni, S Wiessalla, C Schuchardt, RP Baum, B Knäusl, D GeorgA11 Influence of a genetic polymorphism on brain uptake of the dual ABCB1/ABCG2 substrate [11C]tariquidarM Bau

Table of contentsA1 68Ga-PSMA PET/CT in staging and restaging of Prostate Cancer Patients: comparative study with 18F-Choline PET/CTW Langsteger, A Rezaee, W Loidl, HS Geinitz, F Fitz, M Steinmair, G Broinger, L Pallwien-Prettner, M BeheshtiA2 F18 Choline PET - CT: an accurate diagnostic tool for the detection of parathyroid adenoma?L Imamovic, M Beheshti, G Rendl, D Hackl, O Tsybrovsky, M Steinmair, K Emmanuel, F Moinfar, C Pirich, W LangstegerA3 [18F]Fluoro-DOPA-PET/CT in the primary diagnosis of medullary thyroid carcinomaA Bytyqi, G Karanikas, M Mayerhöfer, O Koperek, B Niederle, M HartenbachA4 Variations of clinical PET/MR operations: An international survey on the clinical utilization of PET/MRIT Beyer, K Herrmann, J CzerninA5 Standard Dixon-based attenuation correction in combined PET/MRI: Reproducibility and the possibility of Lean body mass estimationI Rausch, P Rust, MD DiFranco, M Lassen, A Stadlbauer, ME Mayerhöfer, M Hartenbach, M Hacker, T BeyerA6 High resolution digital FDG PET/MRI imaging for assessment of ACL graft viabilityK Binzel, R Magnussen, W Wei, MU Knopp, DC Flanigan, C Kaeding, MV KnoppA7 Using pre-existing hematotoxicity as predictor for severe side effects and number of treatment cycles of Xofigo therapyA Leisser, M Nejabat, M Hartenbach, G Kramer, M Krainer, M Hacker, A HaugA8 QDOSE - comprehensive software solution for internal dose assessmentWencke Lehnert, Karl Schmidt, Sharok Kimiaei, Marcus Bronzel, Andreas KlugeA9 Clinical impact of Time-of-Flight on next-generation digital PET imaging of Yttrium-90 radioactivity following liver radioembolizationCL Wright, K Binzel, J Zhang, Evan Wuthrick, Piotr Maniawski, MV KnoppA10 Snakes in patients! Lessons learned from programming active contours for automated organ segmentationM Blaickner, E Rados, A Huber, M Dulovits, H Kulkarni, S Wiessalla, C Schuchardt, RP Baum, B Knäusl, D GeorgA11 Influence of a genetic polymorphism on brain uptake of the dual ABCB1/ABCG2 substrate [11C]tariquidarM Bau

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".

Inspired by a similar study by Osborne et al. we have conducted a Delphi study among experts to identify key concepts to be taught in engineering and technology education and relevant and meaningful contexts through which these concepts can be taught and learnt. By submitting the outcomes of the Delphi study to a panel of experts in a twoday meeting we were able to add structure to the Delphi results. Thus we reached a concise list of concepts and contexts that can be used to develop curricula for education about engineering and technology as a contribution to technological literacy goals in education., Science Education and Communication, Applied Sciences

Inspired by a similar study by Osborne et al. we have conducted a Delphi study among experts to identify key concepts to be taught in engineering and technology education and relevant and meaningful contexts through which these concepts can be taught and learnt. By submitting the outcomes of the Delphi study to a panel of experts in a twoday meeting we were able to add structure to the Delphi results. Thus we reached a concise list of concepts and contexts that can be used to develop curricula for education about engineering and technology as a contribution to technological literacy goals in education., Science Education and Communication, Applied Sciences

Signatur des Originals: S 36/F00666

Macrotermes michaelsen is a facultative polygynous termite species. Our report provides evidence for an increase of the frequency in polygyny towards a distributional border. We suggest three hypotheses to explain this pattern. Firstly, polygynous colonies have a higher chance to recruit into the mature population. Secondly, alates are more inclined to found colonies co-operatively near a distributional border. Thirdly, at the distributional border the level of intra-colonial conflicts decreases. We provide evidence that the mutilations of queens' antennae may be a measure of ongoing aggression as well as aggression in the past. Our third hypothesis would thus predict that the mutilations of antennae should decrease towards the distributional border, which was not supported by our data.

Our report provides quantitative information on egg production of termites in correlation with the weight of queens and the degree of polygyny of a colony. We suggest that in Macrotermes michaelseni king weight may be used as an independent surrogate for colony age. Queens of a given age (= king of the same weight) were heavier in monogynous colonies than in polygynous colonies. From isolated queens sampled in southern Kenya we found that egg-laying rates increased with queen weight but were independent of the degree of polygyny. Nevertheless, when comparing queens of the same age, the lower weight of queens in polygynous colonies resulted in an individual loss of egg-laying. In sum, however, all nestmate queens together laid more eggs and the colony as a whole had an advantage, at least in the short term.

no abstract

Preionization experiments have been performed on a tokamak by injecting about 80 kW of microwave power at 35 GHz for up to 15 ms. Microwave absorption occurs at the electron cyclotron and upper hybrid resonance frequencies as predicted by theory. Preionization causes substantial (40%) reductions in loop voltage during the initial phase of the tokamak shot. Flux (volt second) savings with preionization are about 30% in the first 2 ms or about 2% of the total flux expenditure in a tokamak shot. The plasma current starts 20 microsec earlier and rises 1.4 times more rapidly in the preionized case. Electron densities of 5 x 10 to the 12th power/cu cm can be sustained with only a toroidal magnetic field during microwave injection. The bulk electron temperature in the preionized plasma is about 10 eV although there are indications of higher electron temperatures (50 eV) in the upper hybrid resonance layer. During the early stages of ohmic heating the preionization is effective in decreasing the peak of the radiated power. (Author)