Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET/MRI.

PURPOSE: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. METHODS: Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. RESULTS: The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. CONCLUSION: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

The effect of MR surface coils on PET quantification in whole-body PET/MR: results from a pseudo-PET/MR phantom study.

PURPOSE: The use of magnetic resonance (MR) radiofrequency (RF) surface coils is a prerequisite for high-quality positron emission tomography (PET)/MR imaging. In lack of in-gantry transmission (TX) sources, the exact position of the RF coils is unknown in PET/MR, and may, therefore, lead to false attenuation correction (AC) of the emission (EM) data. The authors assess lesion and background quantification in AC-PET by mimicking different PET/MR imaging situations using a whole-body (WB) PET-only tomograph. METHODS: Phantom experiments were performed on a PET tomograph with 68 Ge-rod TX sources. First, a 15-cm plastic cylinder was filled uniformly with [18F]-FDG to simulate a head study. Second, a NEMA NU-2001 image quality phantom (35 x 25 x 25 cm3) was filled uniformly with [18F]-FDG to simulate torso imaging. The phantom contained six lesions (10-38 mm diameter, lesion-to-background ratio 6:1) centred around a 5 cm diameter lung insert. EM and TX measurements were acquired with and without MR head (cylinder) and surface (NU-2001 phantom) RF coils in place. The following imaging situations were mimicked in both head and torso phantom studies: (1) PET scan without MR coils in EM and TX for reference, (2) PET scan with coils in both EM and TX, and (3) PET scan with coils in EM but without coils in TX. Two more set-ups were performed for the torso phantom: (4) PET scan with coils in EM only and phantom shifted slightly compared to (3), and (5) PET scan with coils in EM and TX following local displacement of the surface coils. PET EM data (1)-(4) were corrected for attenuation and scatter using cold TX data. Imaging situations (1)-(3) were repeated with the cylinder phantom and head coil in a combined PET/MR prototype system employing template-based AC. RESULTS: Head phantom: In case the MR head coils were not accounted for during AC (3), central and peripheral background activity concentration was underestimated by 13%-19% when compared to the reference setup (1). The effects of MR coil omission during AC was replicated in the repeat study with the combined PET/MR prototype. Torso phantom: All lesions were equally visible on all AC-PET images. The effects of disregarding MR surface RF coils during AC [(3) vs (1)] were 4%, or less. A slightly higher bias was observed when accounting for the RF surface coils that were shifted between EM and TX (5). The effect of coil misalignment and neglect during AC on the quantification of the simulated lungs was insignificant compared to the noise levels in AC-PET. CONCLUSIONS: Unaccounted attenuation from MR surface coils causes a regional bias of AC-PET data in body regions near the MR coils. Bias of central regions was more noticeable in smaller-size objects. In torso studies with body surface coils, the visibility of central lesions on PET was unaffected by MR coils following incomplete AC. Coil misalignment of several cm between emission and attenuation images causes an error that was comparable to that arising from unaccounted MR coil attenuation but small compared to the average standard deviation of the activity concentration levels.

[E-learning in nuclear medicine - a nationwide survey in Germany]. / E-Learning in der Nuklearmedizin: Eine Erhebung an deutschen Universitäten.

AIM: To assess available e-learning concepts and programmes for nuclear medicine at university hospitals in Germany. METHODS: All (34) departments of nuclear medicine at German university hospitals were asked to participate in an anonymized online survey. Questions were categorized into four topics: 1.) clinic and education; 2.) on-site strategies for e-learning; 3.) available e-learning offers and 4.) free text comments on experiences and expectations. All input was reviewed descriptively; free text was analyzed analytically. RESULTS: The response rate was 56% (19/34). 13/19 responses indicated well-defined e-learning strategies, mainly to support frontal teaching courses. Future e-learning perspectives focus on clinical case studies with sufficient imaging materials. Only 7/19 university hospitals operate a centralized e-learning platform (e. g. Moodle). The acceptance of the available e-learning options by the students is considered relatively poor. CONCLUSIONS: Today e-learning concepts for nuclear medicine are available at selected university hospitals only. All responders wish to expand on e-learning but many report the lack of administrative support to do so. These data could be regarded as a basis for discussions of inter-university teaching scenarios.

Multi-modality imaging of uveal melanomas using combined PET/CT, high-resolution PET and MR imaging.

UNLABELLED: We investigated the efficacy of combined FDG-PET/CT imaging for the diagnosis of small-size uveal melanomas and the feasibility of combining separate, high-resolution (HR) FDG-PET with MRI for its improved localization and detection. PATIENTS, METHODS: 3 patients with small-size uveal melanomas (0.2-1.5 ml) were imaged on a combined whole-body PET/CT, a HR brain-PET, and a 1.5 T MRI. Static, contrast-enhanced FDG-PET/CT imaging was performed of head and torso with CT contrast enhancement. HR PET imaging was performed in dynamic mode 0-180 min post-injection of FDG. MRI imaging was performed using a high-resolution small-loop-coil placed over the eye in question with T2-3D-TSE and T1-3D-SE with 18 ml Gd-contrast. Patients had their eyes shaded during the scans. Lesion visibility on high-resolution FDG-PET images was graded for confidence: 1: none, 2: suggestive, 3: clear. Mean tumour activity was calculated for summed image frames that resulted in confidence grades 2 and 3. Whole-body FDG-PET/CT images were reviewed for lesions. PET-MRI and PET/CT-MRI images of the head were co-registered for potentially improved lesion delineation. RESULTS: Whole-body FDG-PET/CT images of 3/3 patients were positive for uveal melanomas and negative for disseminated disease. HR FDG-PET was positive already in the early time frames. One patient exhibited rising tumour activity with increasing uptake time on FDG-PET. MRI images of the eye were co-registered successfully to FDG-PET/CT using a manual alignment approach. CONCLUSIONS: Small-size uveal melanomas can be detected with whole-body FDG-PET/CT. This feasibility study suggests the exploration of HR FDG-PET in order to provide additional diagnostic information on patients with uveal melanomas. First results support extended uptake times and high-sensitivity PET for improved tumour visibility. MRI/PET co-registration is feasible and provides correlated functional and anatomical information that may support alternative therapy regimens.

Quality assessment of unfractionated heparin using 1H nuclear magnetic resonance spectroscopy.

Due to problems, especially anaphylactoid reactions, raised by impure unfractionated heparin the quality assessment of heparin has to be reconsidered. Neither the USP nor the European Pharmacopoeia are able to guarantee the purity of heparin, i.e., the limitation of oversulfated chondroitin sulfate (OSCS) which was found to be the reason for the allergic adverse effects. In the first run the regulatory authorities ask for 1H NMR spectroscopic and capillary electrophoretic measurements in order to characterize the impurity profile of heparin. Using an optimized 1H NMR method the limit of detection for OSCS was found to be 0.1%. In addition, it is possible to reliably quantify both OSCS and dermatan sulfate (DS), the latter being an indicator of poor purification of the unfractionated heparin. Screening of more than 100 heparin samples collected from international markets revealed a high number of samples containing substantial amounts of DS and a number of samples containing OSCS in an amount higher than 0.1%.

Determination of Oversulphated Chondroitin Sulphate and Dermatan Sulphate in unfractionated heparin by (1)H-NMR - Collaborative study for quantification and analytical determination of LoD.

Oversulphated Chondroitin Sulphate (OSCS) and Dermatan Sulphate (DS) in unfractionated heparins can be identified by nuclear magnetic resonance spectrometry (NMR). The limit of detection (LoD) of OSCS is 0.1% relative to the heparin content. This LoD is obtained at a signal-to-noise ratio (S/N) of 2000:1 of the heparin methyl signal. Quantification is best obtained by comparing peak heights of the OSCS and heparin methyl signals. Reproducibility of less than 10% relative standard deviation (RSD) has been obtained. The accuracy of quantification was good.

An international survey on hybrid imaging: do technology advances preempt our training and education efforts?

BACKGROUND: Hybrid PET/CT and PET/MRI are increasingly important technologies in the evaluation of malignancy and require cooperation between radiologists and specialists in molecular imaging. The aim of our study was to probe the mindsets of radiological and nuclear medicine professionals in regard to current hybrid imaging practice and to assess relevant training aspirations and perceived shortfalls, particularly amongst young professionals. In this context, we initiated an international survey on "Hybrid Imaging Training". METHODS: An online survey was prepared on-line and launched on October-2, 2016. It was composed of 17 multiple-choice and open questions regarding the professional background, a perspective on hybrid imaging training efforts and lessons to be learned from disparate craft groups. The survey ran for 2 weeks. We report total responses per category and individual free-text responses. RESULTS: In total, 248 responses were collected with a mean age of all responders of (41 ± 11) y. Overall, 36% were within the target age range of (20-35) y. Across all responders, the majority (72%) commented on there being too few hybrid imaging experts in their country, whereas only 1% said that there were too many. Three quarters of the responders were in favour of a curriculum allowing sub-specialisation in hybrid imaging. With respect to reporting of hybrid imaging, confidence increased with age. The average rating across all responders on the level of cooperation among the two specialties suggested a low overall level of satisfaction. However, the survey feedback indicated the local (on-site) cooperation being somewhat better than the perceived cooperation between the relevant associations on a European level. CONCLUSION: We consider these results to represent an appropriate cross-section of professional opinions of imaging experts across different demographic and hierarchical levels. Collectively they provide evidence supporting a need to address current shortfalls in developing hybrid imaging expertise through national educational plans, and, thus, contribute to helping improve patient care.

A head coil system with an integrated orbiting transmission point source mechanism for attenuation correction in PET/MRI.

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) provides a benefit for diagnostic imaging. Still, attenuation correction (AC) is a challenge in PET/MRI compared to stand-alone PET and PET-computed tomography (PET/CT). In the absence of photonic transmission sources, AC in PET/MRI is usually based on retrospective segmentation of MR images or complex additional MR-sequences. However, most methods available today are still challenged by either the incorporation of cortical bone or substantial anatomical variations of subjects. This leads to a bias in quantification of tracer concentration in PET. Therefore, we have developed a fully integrated transmission source system for PET/MRI of the head to enable direct measurement of attenuation coefficients using external positron emitters, which is the reference standard in AC. Based on a setup called the 'liquid drive' presented by Jones et al (1995) two decades ago, we built a head coil system consisting of an MR-compatible hydraulic system driving a point source on a helical path around a 24-channel MR-receiver coil to perform a transmission scan. Sinogram windowing of the moving source allows for post-injection measurements. The prototype was tested in the Siemens Biograph mMR using a homogeneous water phantom and a phantom with air cavities and a Teflon (PTFE) cylinder. The second phantom was measured both with and without emission activity. For both measurements air, water and Teflon were clearly distinguishable and homogeneous regions of the phantom were successfully reproduced in the AC map. For water the linear attenuation coefficient was measured as (0.096 ± 0.005) cm-1 in accordance with the true physical value. This combined MR head coil and transmission source system is, to our knowledge, the first working example to use an orbiting point source in PET/MRI and may be helpful in providing fully-quantitative PET data in neuro-PET/MRI.

[FDG-PET/CT in oncology. German Guideline]. / FDG-PET/CT in der Onkologie. Leitlinie.

FDG-PET/CT examinations combine metabolic and morphologic imaging within an integrated procedure. Over the past decade PET/CT imaging has gained wide clinical acceptance in the field of oncology. This FDG-PET/CT guideline focuses on indications, data acquisition and processing as well as documentation of FDG-PET/CT examinations in oncologic patients within a clinical and social context specific to Germany. Background information and definitions are followed by examples of clinical and research applications of FDG-PET/CT. Furthermore, protocols for CT scanning (low dose and contrast-enhanced CT) and PET emission imaging are discussed. Documentation and reporting of examinations are specified. Image interpretation criteria and sources of errors are discussed. Quality control for FDG and PET/CT-systems, qualification requirements of personnel as well as legal aspects are presented.

Impact of motion compensation and partial volume correction for 18F-NaF PET/CT imaging of coronary plaque.

Recent studies have suggested that 18F-NaF-PET enables visualization and quantification of plaque micro-calcification in the coronary tree. However, PET imaging of plaque calcification in the coronary arteries is challenging because of the respiratory and cardiac motion as well as partial volume effects. The objective of this work is to implement an image reconstruction framework, which incorporates compensation for respiratory as well as cardiac motion (MoCo) and partial volume correction (PVC), for cardiac 18F-NaF PET imaging in PET/CT. We evaluated the effect of MoCo and PVC on the quantification of vulnerable plaques in the coronary arteries. Realistic simulations (Biograph TPTV, Biograph mCT) and phantom acquisitions (Biograph mCT) were used for these evaluations. Different uptake values in the calcified plaques were evaluated in the simulations, while three 'plaque-type' lesions of 36, 31 and 18 mm3 were included in the phantom experiments. After validation, the MoCo and PVC methods were applied in four pilot NaF-PET patient studies. In all cases, the MoCo-based image reconstruction was performed using the STIR software. The PVC was obtained from a local projection (LP) method, previously evaluated in preclinical and clinical PET. The results obtained show a significant increase of the measured lesion-to-background ratios (LBR) in the MoCo + PVC images. These ratios were further enhanced when using directly the tissue-activities from the LP method, making this approach more suitable for the quantitative evaluation of coronary plaques. When using the LP method on the MoCo images, LBR increased between 200% and 1119% in the simulated data, between 212% and 614% in the phantom experiments and between 46% and 373% in the plaques with positive uptake observed in the pilot patients. In conclusion, we have built and validated a STIR framework incorporating MoCo and PVC for 18F-NaF PET imaging of coronary plaques. First results indicate an improved quantification of plaque-type lesions.

Improvement in the health-related quality-of-life symptoms of hyperparathyroidism is durable on long-term follow-up.

BACKGROUND: Subjective symptoms such as decreased energy, chronic fatigue, and depression are associated with hyperparathyroidism. Studies have shown that these symptoms are improved during short-term follow-up after parathyroidectomy. This study evaluates the durability of this subjective improvement in quality-of-life symptoms in a large population of patients with follow-up greater than 1 year after operation. METHODS: Between 2002 and 2005, 258 patients underwent parathyroidectomy, 100 (81 females and 19 males) of whom were available for this study. The patients were evaluated with a survey based on the Health Outcomes Institute Health Status Questionnaire. Some answers were quantified on a 1 to 6 scale, while others consisted of "yes" or "no" responses. Patients completed a questionnaire prior to parathyroidectomy and postoperatively at 1 month, 3 to 6 months, and 1 to 2 years or greater intervals. Statistical analysis was used to detect changes attributable to parathyroidectomy. A P value <.05 was considered statistically significant. RESULTS: At 1-month follow-up, patients' perceptions of their overall health, energy level, and mood significantly improved. At 6-month follow-up, significant improvements in muscle strength, health, endurance, and relief of anxiety were documented. At the interval of 1 to 2 years, overall health, energy level, endurance, and relief of anxiety were improved. There was no significant decrement in the quality of life in these patients after parathyroidectomy. CONCLUSIONS: Parathyroidectomy for hyperparathyroidism is associated with significant lasting improvement in subjective symptoms. The potential durable improvement in these quality-of-life symptoms is a valid indication for parathyroidectomy.

Continuous glucose monitoring by means of fiber-based, mid-infrared laser spectroscopy.

The application of mid-infrared laser spectroscopy to the reagent-free quantification of the concentration of glucose was investigated using cryogenically cooled lead salt lasers or, alternatively, quantum cascade lasers operating at room temperature. The concentration of glucose in aqueous solutions was quantified by means of fiber-based attenuated total reflection (ATR) spectroscopy (fiber-optical evanescent field analysis, FEFA) as well as fiber-based transmission spectroscopy. Both methods have the potential to be utilized by small fiber sensors, which can be inserted into the subcutaneous tissue in order to continuously measure the local concentration of glucose. In our in vitro experiments, noise-equivalent concentrations as low as 10 mg/dL were achieved. The mid-term stability of the measurement schemes was investigated by means of Allan variance analysis. Based on the research presented in this manuscript, an all-room-temperature measurement scheme using quantum cascade lasers, miniaturized fiber-optic sensors, and pyroelectric detectors appears well suited for the continuous monitoring of glucose concentrations at physiological levels.

Combined 18F-FDG-PET/CT imaging of the head and neck. An approach to metal artifact correction.

UNLABELLED: PET/CT imaging is particularly promising for head/neck malignancies, but dental implants lead to biased CT attenuation and PET activity values following CT-based attenuation correction (CT-AC). OBJECTIVE: Here, we implement a metal artifact correction procedure (MAR) as part of the CT-AC for PET/CT imaging. RESULTS: Phantom studies indicate a maximum quantitative bias in CT and PET of 1000 HU and 30 %, which is reduced to 230 HU and 6 %, respectively following MAR. These results were verified in selected patients. CONCLUSION: Artifacts and biases from dental implants can be reduced in PET/CT imaging by applying a simple MAR as part of the CT-AC.

[Evil radioactivity. Subjective perception of radioactivity in patients with thyroid disease prior to treatment with radioiodine]. / Radioaktivität ist böse: Subjektive Konzepte von Radioaktivität bei Schilddrüsenpatienten vor einer möglichen Radioiodtherapie.

AIM: We assess the perspective of patients with thyroid disease towards radiation and radioactivity by means of a cultural-anthropological approach based on qualitative measures and quantitative scores. From the interviews with the patients we evaluate as to how much radioactivity is accepted as an abstract term or as a benefit within the medical context. PATIENTS, METHODS: 68 patients with autonomously functioning thyroid lesions (35 women, 33 men, 32-81 years) were included in this study. All patients were interviewed in an open dialogue with the principal investigator. Patients were asked to describe their attitude towards radioactivity in general and towards radioiodine therapy in particular. Patients were asked to use a scoring system (1 = positive, 5 = negative) to quantify their attitudes. RESULTS: The responses of all patients towards radioactivity in general were heterogeneous with most responses reflecting a negative perception. Many patients expressed their associated fears about atomic energy, malignant diseases and radioactive contamination. The scoring system reflected a mostly negative opinion base. However, patients became more positive once they assumed an immediate benefit of radioactivity for the treatment of their own disease (p = 0.01). CONCLUSIONS: Knowing about significant differences in patient's perception about radioactivity in general or in the clinical context may help to optimise and tailor the initial, pre-therapeutical interview towards the patient.

32nd International Austrian Winter Symposium : Zell am See, the Netherlands. 20-23 January 2016.

TABLE OF CONTENTS: A1 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 Bauer, B Wulkersdorfer, W Wadsak, C Philippe, H Haslacher, M Zeitlinger, O LangerA12 Outcome prediction of temporal lobe epilepsy surgery from P-glycoprotein activity. Pooled analysis of (R)-[11C]-verapamil PET data from two European centresM Bauer, M Feldmann, R Karch, W Wadsak, M Zeitlinger, MJ Koepp, M-C Asselin, E Pataraia, O LangerA13 In-vitro and in-vivo characterization of [18F]FE@SNAP and derivatives for the visualization of the melanin concentrating hormone receptor 1M Zeilinger, C Philippe, M Dumanic, F Pichler, J Pilz, M Hacker, W Wadsak, M MitterhauserA14 Reducing time in quality control leads to higher specific radioactivity of short-lived radiotracersL Nics, B Steiner, M Hacker, M Mitterhauser, W WadsakA15 In vitro 11C-erlotinib binding experiments in cancer cell lines with epidermal growth factor receptor mutationsA Traxl, Thomas Wanek, Kushtrim Kryeziu, Severin Mairinger, Johann Stanek, Walter Berger, Claudia Kuntner, Oliver LangerA16 7-[11C]methyl-6-bromopurine, a PET tracer to measure brain Mrp1 function: radiosynthesis and first PET evaluation in miceS Mairinger, T Wanek, A Traxl, M Krohn, J Stanek, T Filip, M Sauberer, C Kuntner, J Pahnke, O LangerA17 18F labeled azidoglucose derivatives as "click" agents for pretargeted PET imagingD Svatunek, C Denk, M Wilkovitsch, T Wanek, T Filip, C Kuntner-Hannes, J Fröhlich, H MikulaA18 Bioorthogonal tools for PET imaging: development of radiolabeled 1,2,4,5-TetrazinesC Denk, D Svatunek, T Wanek, S Mairinger, J Stanek, T Filip, J Fröhlich, H Mikula, C Kuntner-HannesA19 Preclinical evaluation of [18F]FE@SUPPY- a new PET-tracer for oncologyT Balber, J Singer, J Fazekas, C Rami-Mark, N Berroterán-Infante, E Jensen-Jarolim, W Wadsak, M Hacker, H Viernstein, M MitterhauserA20 Investigation of Small [18F]-Fluoroalkylazides for Rapid Radiolabeling and In Vivo Click ChemistryC Denk, D Svatunek, B Sohr, H Mikula, J Fröhlich, T Wanek, C Kuntner-Hannes, T FilipA21 Microfluidic 68Ga-radiolabeling of PSMA-HBED-CC using a flow-through reactorS Pfaff, C Philippe, M Mitterhauser, M Hartenbach, M Hacker, W WadsakA22 Influence of 24-nor-ursodeoxycholic acid on hepatic disposition of [18F]ciprofloxacin measured with positron emission tomographyT Wanek, E Halilbasic, M Visentin, S Mairinger, B Stieger, C Kuntner, M Trauner, O LangerA23 Automated 18F-flumazenil production using chemically resistant disposable cassettesP Lam, M Aistleitner, R Eichinger, C ArtnerA24 Similarities and differences in the synthesis and quality control of 177Lu-DOTA-TATE, 177Lu -HA-DOTA-TATE and 177Lu-DOTA-PSMA (PSMA-617)H Eidherr, C Vraka, A Haug, M Mitterhauser, L Nics, M Hartenbach, M Hacker, W WadsakA25 68Ga- and 177Lu-labelling of PSMA-617H Kvaternik, R Müller, D Hausberger, C Zink, RM AignerA26 Radiolabelling of liposomes with 67Ga and biodistribution studies after administration by an aerosol inhalation systemU Cossío, M Asensio, A Montes, S Akhtar, Y te Welscher, R van Nostrum, V Gómez-Vallejo, J LlopA27 Fully automated quantification of DaTscan SPECT: Integration of age and gender differencesF VandeVyver, T Barclay, N Lippens, M TrochA28 Lesion-to-background ratio in co-registered 18F-FET PET/MR imaging - is it a valuable tool to differentiate between low grade and high grade brain tumor?L Hehenwarter, B Egger, J Holzmannhofer, M Rodrigues-Radischat, C PirichA29 [11C]-methionine PET in gliomas - a retrospective data analysis of 166 patientsN Pötsch, I Rausch, D Wilhelm, M Weber, J Furtner, G Karanikas, A Wöhrer, M Mitterhauser, M Hacker, T Traub-WeidingerA30 18F-Fluorocholine versus 18F-Fluorodeoxyglucose for PET/CT imaging in patients with relapsed or progressive multiple myeloma: a pilot studyT Cassou-Mounat, S Balogova, V Nataf, M Calzada, V Huchet, K Kerrou, J-Y Devaux, M Mohty, L Garderet, J-N TalbotA31 Prognostic benefit of additional SPECT/CT in sentinel lymph node mapping of breast cancer patientsS Stanzel, G Pregartner, T Schwarz, V Bjelic-Radisic, B Liegl-Atzwanger, R AignerA32 Evaluation of diagnostic value of TOF-18F-FDG PET/CT in patients with suspected pancreatic cancerS Stanzel, F Quehenberger, RM AignerA33 New quantification method for diagnosis of primary hyperpatahyroidism lesions and differential diagnosis vs thyropid nodular disease in dynamic scintigraphyA Koljevic Markovic, Milica Jankovic, V Miler Jerkovic, M Paskas, G Pupic, R Dzodic, D PopovicA34 A rare case of diffuse pancreatic involvement in patient with merkel cell carcinoma detected by 18F-FDGMC Fornito, D FamiliariA35 TSH-stimulated 18F-FDG PET/CT in the diagnosis of recurrent/metastatic radioiodine-negative differentiated thyroid carcinomas in patients with various thyroglobuline levelsP Koranda, H Polzerová, I Metelková, L Henzlová, R Formánek, E Buriánková, M KamínekA36 Breast Dose from lactation following I131 treatmentWH Thomson, C LewisA37 A new concept for performing SeHCAT studies with the gamma cameraWH Thomson, J O'Brien, G James, A NotghiA38 Whole body F-18-FDG-PET and tuberculosis: sensitivity compared to x-ray-CTH Huber, I Stelzmüller, R Wunn, M Mandl, F Fellner, B Lamprecht, M GabrielA39 Emerging role 18F-FDG PET-CT in the diagnosis and follow-up of the infection in heartware ventricular assist system (HVAD)MC Fornito, G LeonardiA40 Validation of Poisson resampling softwareWH Thomson, J O'Brien, G JamesA41 Protection of PET nuclear medicine personnel: problems in satisfying dose limit requirementsJ Hudzietzová, J Sabol, M Fülöp.

Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tübingen, Germany.

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

Treatment with annexin V increases immunogenicity of apoptotic human T-cells in Balb/c mice.

Exposure of phosphatidylserine on the outer leaflet of the cytoplasmic membrane is an early event during apoptotic cell death and serves as a recognition signal for phagocytes. Usually the clearance of apoptotic cells does not initiate inflammation or immune response. We investigated the immune response in Balb/c mice towards apoptotic human T-cells. Animals injected with apoptotic cells showed significantly reduced humoral immune responses, especially Th1-dependent IgG2a titres, compared to controls immunised with viable cells. However, treatment of apoptotic cells with annexin V (AxV) significantly increased the humoral immune response. AxV binds with high affinity to anionic phospholipids and as a result interferes with the phosphatidylserine recognition by phagocytes. Our results indicate that AxV treatment may be used to increase the efficiency of apoptotic cell-based vaccines, e.g. some tumour vaccines.

Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death.

The phagocytosis of dying cells is an integral feature of apoptosis and necrosis. There are many receptors involved in recognition of dying cells, however, the molecular mechanisms of the scavenging process remain elusive. The activation by necrotic cells of complement is well established, however, the importance of complement in the scavenging process of apoptotic cells was just recently described. Here we report that the complement components C3 and C4 immediately bound to necrotic cells. The binding of complement was much higher for lymphocytes compared to granulocytes. In case of apoptotic cell death complement binding was a rather late event, which in lymphocytes was preceded by secondary necrosis. Taken together complement binding is an immediate early feature of necrosis and a rather late event during apoptotic cell death. We conclude that complement may serve as an opsonin for fragments of apoptotic cells that have escaped regular scavenging mechanisms.