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Purpose: The adenosine A 2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A 2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A 2A receptor radiotracer and report herein the preclinical evaluation of [ 18 F]FLUDA, a deuterated isotopologue of [ 18 F]FESCH., Methods: [ 18 F]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: [ 18 F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72-180 GBq/μmol. Autoradiography proved A 2A receptor-specific accumulation of [ 18 F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [ 18 F]FLUDA compared to that of [ 18 F]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 [ 18 F]FLUDA towards striatal A 2A 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 [ 18 F]FLUDA., Conclusions: The new radiotracer [ 18 F]FLUDA is suitable to detect the availability of the A 2A receptor in the brain with high target specificity. It is regarded ready for human application.

Multimodality imaging has emerged from a vision thirty years ago to routine clinical use today. Positron emission tomography (PET)/magnetic resonance imaging (MRI) is still relatively new in this arena and particularly suitable for clinical research and technical development. PET/MRI-guidance for interventions opens up opportunities for novel treatments but at the same time demands certain technical and organizational requirements to be fulfilled. In this work, we aimed to demonstrate a practical setting and potential application of PET/MRI guidance of interventional procedures. The superior quantitative physiologic information of PET, the various unique imaging characteristics of MRI, and the reduced radiation exposure are the most relevant advantages of this technique. As a noninvasive interventional tool, focused ultrasound (FUS) ablation of tumor cells would benefit from PET/MRI for diagnostics, treatment planning and intervention. Yet, technical limitations might impeed preclinical research, given that PET/MRI sites are per se not designed as interventional suites. Nonetheless, several approaches have been offered in the past years to upgrade MRI suites for interventional purposes. Taking advantage of state of the art and easy-to-use technology it is possible to create a supporting infrastructure that is suitable for broad preclinical adaption. Several aspects are to be addressed, including remote control of the imaging system, display of the imaging results, communication technology, and implementation of additional devices such as a FUS platform and an MR-compatible robotic system for positioning of the FUS equipment. Feasibility could be demostrated with an examplary experimental setup for interventional PET/MRI. Most PET/MRI sites could allow for interventions with just a few add-ons and modifications, such as comunication, in room image display and sytems control. By unlocking this feature, and driving preclinical research in interventional PET/MRI, translation of the protocol and methodology into clinical settings seems feasible.

The expression of monocarboxylate transporters (MCTs) is linked to pathophysiological changes in diseases, including cancer, such that MCTs could potentially serve as diagnostic markers or therapeutic targets. We recently developed [ 18 F]FACH as a radiotracer for non-invasive molecular imaging of MCTs by positron emission tomography (PET). The aim of this study was to evaluate further the specificity, metabolic stability, and pharmacokinetics of [ 18 F]FACH in healthy mice and piglets. We measured the [ 18 F]FACH plasma protein binding fractions in mice and piglets and the specific binding in cryosections of murine kidney and lung. The biodistribution of [ 18 F]FACH was evaluated by tissue sampling ex vivo and by dynamic PET/MRI in vivo, with and without pre-treatment by the MCT inhibitor α-CCA-Na or the reference compound, FACH-Na. Additionally, we performed compartmental modelling of the PET signal in kidney cortex and liver. Saturation binding studies in kidney cortex cryosections indicated a K D of 118 ± 12 nM and B max of 6.0 pmol/mg wet weight. The specificity of [ 18 F]FACH uptake in the kidney cortex was confirmed in vivo by reductions in AUC 0-60min after pre-treatment with α-CCA-Na in mice (-47%) and in piglets (-66%). [ 18 F]FACH was metabolically stable in mouse, but polar radio-metabolites were present in plasma and tissues of piglets. The [ 18 F]FACH binding potential (BP ND ) in the kidney cortex was approximately 1.3 in mice. The MCT1 specificity of [ 18 F]FACH uptake was confirmed by displacement studies in 4T1 cells. [ 18 F]FACH has suitable properties for the detection of the MCTs in kidney, and thus has potential as a molecular imaging tool for MCT-related pathologies, which should next be assessed in relevant disease models.

These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET imaging is being increasingly used to supplement MRI in the clinical management of glioma. The aim of these standards/guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting and reporting the results of brain PET imaging in patients with glioma to achieve a high-quality imaging standard for PET using FDG and the radiolabelled amino acids MET, FET and FDOPA. This will help promote the appropriate use of PET imaging and contribute to evidence-based medicine that may improve the diagnostic impact of this technique in neurooncological practice. The present document replaces a former version of the guidelines published in 2006 (Vander Borght et al. Eur J Nucl Med Mol Imaging. 33:1374-80, 2006), and supplements a recent evidence-based recommendation by the PET-RANO working group and EANO on the clinical use of PET imaging in patients with glioma (Albert et al. Neuro Oncol. 18:1199-208, 2016). The information provided should be taken in the context of local conditions and regulations.

Background: Current research diagnostic criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD include biomarkers to supplement clinical testing. Recently, we demonstrated that dual time-point [18F]FBB PET is able to deliver both blood flow and amyloid-β (Aβ) load surrogates., Objective: The aim of this study was to investigate whether these surrogates can be utilized as AD biomarkers., Methods: 112 subjects (41 with MCI, 50 with probable/possible AD, 21 with other dementias) underwent dual time-point [18F]FBB PET. Data were visually and relative quantitatively (Herholz scores for the early and composite SUVRs for the late PET data) analyzed., Results: In the early images AD-typical patterns were present in 42% /27% /33% of probable/possible AD/MCI/other dementia cases. In late [18F]FBB PET, 42% /29% /38% of probable/possible AD/ MCI/other dementia cases were Aβ-positive. 17% of the MCIs were categorized as "MCI due to AD-high likelihood", 44% of the probable ADs as "probable AD with high evidence of AD pathophysiological process" and 28% of the possible ADs as "possible AD with evidence of AD pathophysiological process". 27% of all subjects showed a positive diagnostic and progression biomarker. Herholz scores were lower (0.85±0.05 versus 0.88±0.04, p = 0.015) for probable/possible AD versus MCI. Composite late phase SUVRs were significantly higher (1.65±0.23 versus 1.15±0.17, p < 0.005) in Aβ-positive versus Aβ-negative patients. Herholz and MMSE scores were positively correlated (R = 0.30 p = 0.006)., Conclusion: Dual time-point [18F]FBB PET provides dual biomarker information which enables to categorize MCI and AD dementia patients according to established diagnostic criteria. Thus, dual time-point [18F]FBB PET has great potential to supplement diagnostic dementia workups.

Objective: To compare cardiac left ventricular (LV) parameters in simultaneously acquired hybrid fluorine-18-fluorodeoxyglucose ([18F] FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with residual tracer activity of upstream PET/CT., Methods: Twenty-nine patients (23 men, age 58±17 years) underwent cardiac PET/MRI either directly after a non-cardiac PET/CT with homogenous cardiac [18F] FDG uptake (n=20) or for viability assessment (n=9). Gated cardiac [18F] FDG PET and cine MR sequences were acquired simultaneously and evaluated blinded to the cross-imaging results. Image quality (IQ), end-diastolic (LVEDV), end-systolic volume (LVESV), ejection fraction (LVEF) and myocardial mass (LVMM) were measured. Pearson correlation and intraclass correlation coefficient (ICC), regression and a Bland-Altman analysis were assessed., Results: Except LVMM, volumetric and functional LV parameters demonstrated high correlations (LVESV: r=0.97, LVEDV: r=0.95, LVEF: r=0.91, LVMM: r=0.87, each p<0.05), but wide limits of agreement (LOA) for LVEDV (-25.3-82.5ml); LVESV (-33.1-72.7ml); LVEF (-18.9-14.8%) and LVMM (-78.2-43.2g). Intra- and interobserver reliability were very high (ICC≥0.95) for all parameters, except for MR-LVEF (ICC=0.87). PET-IQ (0-3) was high (mean: 2.2±0.9) with significant influence on LVMM calculations only., Conclusion: In simultaneously acquired cardiac PET/MRI data, LVEDV, LVESV and LVEF show good agreement. However, the agreement seems to be limited if cardiac PET/MRI follows PET/CT and only the residual activity is used., Key Points: • [ 18 F] FDG PET-MRI is feasible with residual [ 18 F] FDG activity in patients with homogenous cardiac uptake. • Cardiac volumes and function assessed by PET/MRI show good agreement. • LVEDV and LVESV are underestimated; PET overestimates LVMM and LVEF. • Cardiac PET and MRI data correlate better when acquired simultaneously than sequentially. • PET and MRI should not assess LV parameters interchangeably.

This paper highlights the origins of combined positron emission tomography (PET) and magnetic resonance imaging (MRI) whole-body systems that were first introduced for applications in humans in 2010. This text first covers basic aspects of each imaging modality before describing the technical and methodological challenges of combining PET and MRI within a single system. After several years of development, combined and even fully-integrated PET/MRI systems have become available and made their way into the clinic. This multi-modality imaging system lends itself to the advanced exploration of diseases to support personalized medicine in a long run. To that extent, this paper provides an introduction to PET/MRI methodology and important technical solutions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Quantitative positron emission tomography/computed tomography (PET/CT) can be used as diagnostic or prognostic tools (i.e. single measurement) or for therapy monitoring (i.e. longitudinal studies) in multicentre studies. Use of quantitative parameters, such as standardized uptake values (SUVs), metabolic active tumor volumes (MATVs) or total lesion glycolysis (TLG), in a multicenter setting requires that these parameters be comparable among patients and sites, regardless of the PET/CT system used. This review describes the motivations and the methodologies for quantitative PET/CT performance harmonization with emphasis on the EANM Research Ltd. (EARL) Fluorodeoxyglucose (FDG) PET/CT accreditation program, one of the international harmonization programs aiming at using FDG PET as a quantitative imaging biomarker. In addition, future accreditation initiatives will be discussed. The validation of the EARL accreditation program to harmonize SUVs and MATVs is described in a wide range of tumor types, with focus on therapy assessment using either the European Organization for Research and Treatment of Cancer (EORTC) criteria or PET Evaluation Response Criteria in Solid Tumors (PERCIST), as well as liver-based scales such as the Deauville score. Finally, also presented in this paper are the results from a survey across 51 EARL-accredited centers reporting how the program was implemented and its impact on daily routine and in clinical trials, harmonization of new metrics such as MATV and heterogeneity features.

Purpose: Established Alzheimer's disease (AD) biomarker concepts classify into amyloid pathology and neuronal injury biomarkers, while recent alternative concepts classify into diagnostic and progression AD biomarkers. However, combined amyloid positron emission tomography/magnetic resonance imaging (PET/MRI) offers the chance to obtain both biomarker category read-outs within one imaging session, with increased patient as well as referrer convenience. The aim of this pilot study was to investigate this matter for the first time., Methods: 100 subjects (age 70 ± 10 yrs, 46 female), n = 51 with clinically defined mild cognitive impairment (MCI), n = 44 with possible/probable AD dementia, and n = 5 with frontotemporal lobe degeneration, underwent simultaneous [ 18 F]florbetaben or [ 11 C]PIB PET/MRI (3 Tesla Siemens mMR). Brain amyloid load, mesial temporal lobe atrophy (MTLA) by means of the Scheltens scale, and other morphological brain pathologies were scored by respective experts. The patients/caregivers as well as the referrers were asked to assess on a five-point scale the convenience related to the one-stop-shop PET and MRI approach., Results: In three subjects, MRI revealed temporal lobe abnormalities other than MTLA. According to the National Institute on Aging-Alzheimer's Association classification, the combined amyloid-beta PET/MRI evaluation resulted in 31 %, 45 %, and 24 % of the MCI subjects being categorized as "MCI-unlikely due to AD", "MCI due to AD-intermediate likelihood", and "MCI due to AD-high likelihood", respectively. 50 % of the probable AD dementia patients were categorized as "High level of evidence of AD pathophysiological process", and 56 % of the possible AD dementia patients as "Possible AD dementia - with evidence of AD pathophysiological process". With regard to the International Working Group 2 classification, 36 subjects had both positive diagnostic and progression biomarkers. The patient/caregiver survey revealed a gain of convenience in 88 % of responders as compared to a theoretically separate PET and MR imaging. In the referrer survey, an influence of the combined amyloid-beta PET/MRI on the final diagnosis was reported by 82 % of responders, with a referrer acceptance score of 3.7 ± 1.0 on a 5-point scale., Conclusion: Simultaneous amyloid PET/MRI is feasible and provides imaging biomarkers of all categories which are able to supplement the clinical diagnosis of MCI due to AD and that of AD dementia. Further, patient and referrer convenience is improved by this one-stop-shop imaging approach.

The enantiomers of [(18)F]fluspidine, recently developed for imaging of σ₁ receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(-)-[(18)F]fluspidine and (R)-(+)-[(18)F]fluspidine from ex vivo biodistribution and PET/MRI data in mice after extrapolation to the human scale. In addition, we validated the preclinical results by performing a first-in-human PET/CT study using (S)-(-)-[(18)F]fluspidine. Based on the respective time-activity curves, we calculated using OLINDA the particular organ doses (ODs) and effective doses (EDs). The ED values of (S)-(-)-[(18)F]fluspidine and (R)-(+)-[(18)F]fluspidine differed significantly with image-derived values obtained in mice with 12.9 μSv/MBq and 14.0 μSv/MBq (p < 0.025), respectively. A comparable ratio was estimated from the biodistribution data. In the human study, the ED of (S)-(-)-[(18)F]fluspidine was calculated as 21.0 μSv/MBq. Altogether, the ED values for both [(18)F]fluspidine enantiomers determined from the preclinical studies are comparable with other (18)F-labeled PET imaging agents. In addition, the first-in-human study confirmed that the radiation risk of (S)-(-)-[(18)F]fluspidine imaging is within acceptable limits. However, as already shown for other PET tracers, the actual ED of (S)-(-)-[(18)F]fluspidine in humans was underestimated by preclinical imaging which needs to be considered in other first-in-human studies.

Objective: We assess inter- and intra-subject variability of magnetic resonance (MR)-based attenuation maps (MRμMaps) of human subjects for state-of-the-art positron emission tomography (PET)/MR imaging systems., Materials and Methods: Four healthy male subjects underwent repeated MR imaging with a Siemens Biograph mMR, Philips Ingenuity TF and GE SIGNA PET/MR system using product-specific MR sequences and image processing algorithms for generating MRμMaps. Total lung volumes and mean attenuation values in nine thoracic reference regions were calculated. Linear regression was used for comparing lung volumes on MRμMaps. Intra- and inter-system variability was investigated using a mixed effects model., Results: Intra-system variability was seen for the lung volume of some subjects, (p = 0.29). Mean attenuation values across subjects were significantly different (p < 0.001) due to different segmentations of the trachea. Differences in the attenuation values caused noticeable intra-individual and inter-system differences that translated into a subsequent bias of the corrected PET activity values, as verified by independent simulations., Conclusion: Significant differences of MRμMaps generated for the same subjects but different PET/MR systems resulted in differences in attenuation correction factors, particularly in the thorax. These differences currently limit the quantitative use of PET/MR in multi-center imaging studies.

Purpose: Integrated positron emission tomography/magnetic resonance (PET/MR) systems derive the PET attenuation correction (AC) from dedicated MR sequences. While MR-AC performs reasonably well in clinical patient imaging, it may fail for phantom-based quality control (QC). The authors assess the applicability of different protocols for PET QC in multicenter PET/MR imaging., Methods: The National Electrical Manufacturers Association NU 2 2007 image quality phantom was imaged on three combined PET/MR systems: a Philips Ingenuity TF PET/MR, a Siemens Biograph mMR, and a GE SIGNA PET/MR (prototype) system. The phantom was filled according to the EANM FDG-PET/CT guideline 1.0 and scanned for 5 min over 1 bed. Two MR-AC imaging protocols were tested: standard clinical procedures and a dedicated protocol for phantom tests. Depending on the system, the dedicated phantom protocol employs a two-class (water and air) segmentation of the MR data or a CT-based template. Differences in attenuation- and SUV recovery coefficients (RC) are reported. PET/CT-based simulations were performed to simulate the various artifacts seen in the AC maps (μ-map) and their impact on the accuracy of phantom-based QC., Results: Clinical MR-AC protocols caused substantial errors and artifacts in the AC maps, resulting in underestimations of the reconstructed PET activity of up to 27%, depending on the PET/MR system. Using dedicated phantom MR-AC protocols, PET bias was reduced to -8%. Mean and max SUV RC met EARL multicenter PET performance specifications for most contrast objects, but only when using the dedicated phantom protocol. Simulations confirmed the bias in experimental data to be caused by incorrect AC maps resulting from the use of clinical MR-AC protocols., Conclusions: Phantom-based quality control of PET/MR systems in a multicenter, multivendor setting may be performed with sufficient accuracy, but only when dedicated phantom acquisition and processing protocols are used for attenuation correction.

Prospective studies on magnetic resonance imaging (MRI)-guided systemic thrombolysis >4.5 hours after stroke onset did not reach their primary end points. It was discussed and observed in post hoc data re-assessment that this was partly because of limited MRI accuracy to measure critical hypoperfusion. We report the first cases of simultaneous [(15)O]H2O-positron emission tomography (PET)/MRI in stroke patients and an ovine model. Discrepancies between simultaneously obtained PET and MRI readouts were observed that might explain the above current limitations of stroke MRI. By offering highly complementary information, [(15)O]H2O-PET/MRI might help to identify critically hypoperfused tissue resulting in an improved patient stratification in thrombolysis trials.

α4β2* nicotinic receptors (α4β2* nAChRs) could provide a biomarker in neuropsychiatric disorders (e.g., Alzheimer's and Parkinson's diseases, depressive disorders, and nicotine addiction). However, there is a lack of α4β2* nAChR specific PET radioligands with kinetics fast enough to enable quantification of nAChR within a reasonable time frame. Following on from promising preclinical results, the aim of the present study was to evaluate for the first time in humans the novel PET radioligand (-)-[(18)F]Flubatine, formerly known as (-)-[(18)F]NCFHEB, as a tool for α4β2* nAChR imaging and in vivo quantification. Dynamic PET emission recordings lasting 270min were acquired on an ECAT EXACT HR+ scanner in 12 healthy male non-smoking subjects (71.0±5.0years) following the intravenous injection of 353.7±9.4MBq of (-)-[(18)F]Flubatine. Individual magnetic resonance imaging (MRI) was performed for co-registration. PET frames were motion-corrected, before the kinetics in 29 brain regions were characterized using 1- and 2-tissue compartment models (1TCM, 2TCM). Given the low amounts of metabolite present in plasma, we tested arterial input functions with and without metabolite corrections. In addition, pixel-based graphical analysis (Logan plot) was used. The model's goodness of fit, with and without metabolite correction was assessed by Akaike's information criterion. Model parameters of interest were the total distribution volume VT (mL/cm(3)), and the binding potential BPND relative to the corpus callosum, which served as a reference region. The tracer proved to have high stability in vivo, with 90% of the plasma radioactivity remaining as untransformed parent compound at 90min, fast brain kinetics with rapid uptake and equilibration between free and receptor-bound tracer. Adequate fits of brain TACs were obtained with the 1TCM. VT could be reliably estimated within 90min for all regions investigated, and within 30min for low-binding regions such as the cerebral cortex. The rank order of VT by region corresponded well with the known distribution of α4β2* receptors (VT [thalamus] 27.4±3.8, VT [putamen] 12.7±0.9, VT [frontal cortex] 10.0±0.8, and VT [corpus callosum] 6.3±0.8). The BPND, which is a parameter of α4β2* nAChR availability, was 3.41±0.79 for the thalamus, 1.04±0.25 for the putamen and 0.61±0.23 for the frontal cortex, indicating high specific tracer binding. Use of the arterial input function without metabolite correction resulted in a 10% underestimation in VT, and was without important biasing effects on BPND. Altogether, kinetics and imaging properties of (-)-[(18)F]Flubatine appear favorable and suggest that (-)-[(18)F]Flubatine is a very suitable and clinically applicable PET tracer for in vivo imaging of α4β2* nAChRs in neuropsychiatric disorders., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study explores the possibility of using simultaneous positron emission tomography--magnetic resonance imaging (PET-MRI) to estimate the lean body mass (LBM) in order to obtain a standardized uptake value (SUV) which is less dependent on the patients' adiposity. This approach is compared to (1) the commonly-used method based on a predictive equation for LBM, and (2) to using an LBM derived from PET-CT data. It is hypothesized that an MRI-based correction of SUV provides a robust method due to the high soft-tissue contrast of MRI. A straightforward approach to calculate an MRI-derived LBM is presented. It is based on the fat and water images computed from the two-point Dixon MRI primarily used for attenuation correction in PET-MRI. From these images, a water fraction was obtained for each voxel. Averaging over the whole body yielded the weight-normalized LBM. Performance of the new approach in terms of reducing variations of (18)F-Fludeoxyglucose SUVs in brain and liver across 19 subjects was compared with results using predictive methods and PET-CT data to estimate the LBM. The MRI-based method reduced the coefficient of variation of SUVs in the brain by 41 ± 10% which is comparable to the reduction by the PET-CT method (35 ± 10%). The reduction of the predictive LBM method was 29 ± 8%. In the liver, the reduction was less clear, presumably due to other sources of variation. In conclusion, employing the Dixon data in simultaneous PET-MRI for calculation of lean body mass provides a brain SUV which is less dependent on patient adiposity. The reduced dependency is comparable to that obtained by CT and predictive equations. Therefore, it is more comparable across patients. The technique does not impose an overhead in measurement time and is straightforward to implement.

Purpose: (18)F-Florbetaben is a positron emission tomography (PET) tracer indicated for imaging cerebral beta-amyloid deposition in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive decline. The present study examined ethnic comparability of the plasma pharmacokinetics, which is the input to the brain, between Caucasian and Japanese subjects., Methods: Two identical phase I trials were performed in 18 German and 18 Japanese healthy volunteers to evaluate the plasma pharmacokinetics of a single dose of 300 MBq (18)F-florbetaben, either of low (≤5 μg, LD) or high (50-55 μg, HD) mass dose. Pharmacokinetic parameters were evaluated based on the total (18)F radioactivity measurements in plasma followed by metabolite analysis using radio-HPLC., Results: The pharmacokinetics of (18)F-florbetaben was characterized by a rapid elimination from plasma. The dose-normalized areas under the curve of (18)F-florbetaben in plasma as an indicator of the input to the brain were comparable between Germans (LD: 0.38 min/l, HD: 0.55 min/l) and Japanese (LD: 0.35 min/l, HD: 0.45 min/l) suggesting ethnic similarity, and the mass dose effect was minimal. A polar metabolite fraction was the main radiolabelled degradation product in plasma and was also similar between the doses and the ethnic groups., Conclusion: Absence of a difference in the pharmacokinetics of (18)F-florbetaben in Germans and Japanese has warranted further global development of the PET imaging agent.

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.

Use of PET/MR in children has not previously been reported, to the best of our knowledge. Children with systemic malignancies may benefit from the reduced radiation exposure offered by PET/MR. We report our initial experience with PET/MR hybrid imaging and our current established sequence protocol after 21 PET/MR studies in 15 children with multifocal malignant diseases. The effective dose of a PET/MR scan was only about 20% that of the equivalent PET/CT examination. Simultaneous acquisition of PET and MR data combines the advantages of the two previously separate modalities. Furthermore, the technique also enables whole-body diffusion-weighted imaging (DWI) and statements to be made about the biological cellularity and nuclear/cytoplasmic ratio of tumours. Combined PET/MR saves time and resources. One disadvantage of PET/MR is that in order to have an effect, a significantly longer examination time is needed than with PET/CT. In our initial experience, PET/MR has turned out to be an unexpectedly stable and reliable hybrid imaging modality, which generates a complementary diagnostic study of great additional value.

The implementation of hybrid imaging systems requires thorough and anticipatory planning at local and regional levels. For installation of combined positron emission and magnetic resonance imaging systems (PET/MRI), a number of physical and constructional provisions concerning shielding of electromagnetic fields (RF- and high-field) as well as handling of radionuclides have to be met, the latter of which includes shielding for the emitted 511 keV gamma rays. Based on our experiences with a SIEMENS Biograph mMR system, a step-by-step approach is required to allow a trouble-free installation. In this article, we present a proposal for a standardized step-by-step plan to accomplish the installation of a combined PET/MRI system. Moreover, guidelines for the smooth operation of combined PET/MRI in an integrated research and clinical setting will be proposed. Overall, the most important preconditions for the successful implementation of PET/MRI in an integrated research and clinical setting is the interdisciplinary target-oriented cooperation between nuclear medicine, radiology, and all referring and collaborating institutions at all levels of interaction (personnel, imaging protocols, reporting, selection of the data transfer and communication methods).

Purpose: Integrated whole-body PET/MRI tomographs have become available. PET/MR imaging has the potential to supplement, or even replace combined PET/CT imaging in selected clinical indications. However, this is true only if methodological pitfalls and image artifacts arising from novel MR-based attenuation correction (MR-AC) are fully understood., Results: Here we present PET/MR image artifacts following routine MR-AC, as most frequently observed in clinical operations of an integrated whole-body PET/MRI system., Conclusion: A clinical adoption of integrated PET/MRI should entail the joint image display and interpretation of MR data, MR-based attenuation maps and uncorrected plus attenuation-corrected PET images in order to recognize potential pitfalls from MR-AC and to ensure clinically accurate image interpretation.

Unlabelled: 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.

Purpose: Complementing clinical findings with those generated by biomarkers--such as β-amyloid-targeted positron emission tomography (PET) imaging--has been proposed as a means of increasing overall accuracy in the diagnosis of Alzheimer's disease (AD). Florbetaben ([(18)F]BAY 94-9172) is a novel β-amyloid PET tracer currently in global clinical development. We present the results of a proof of mechanism study in which the diagnostic efficacy, pharmacokinetics, safety and tolerability of florbetaben were assessed. The value of various quantitative parameters derived from the PET scans as potential surrogate markers of cognitive decline was also investigated., Methods: Ten patients with mild-moderate probable AD (DSM-IV and NINCDS-ADRDA criteria) and ten age-matched (≥ 55 years) healthy controls (HCs) were administered a single dose of 300 MBq florbetaben, which contained a tracer mass dose of < 5 μg. The 70-90 min post-injection brain PET data were visually analysed by three blinded experts. Quantitative assessment was also performed via MRI-based, anatomical sampling of predefined volumes of interest (VOI) and subsequent calculation of standardized uptake value (SUV) ratios (SUVRs, cerebellar cortex as reference region). Furthermore, single-case, voxelwise analysis was used to calculate individual "whole brain β-amyloid load"., Results: Visual analysis of the PET data revealed nine of the ten AD, but only one of the ten HC brains to be β-amyloid positive (p = 0.001), with high inter-reader agreement (weighted kappa ≥ 0.88). When compared to HCs, the neocortical SUVRs were significantly higher in the ADs (with descending order of effect size) in frontal cortex, lateral temporal cortex, occipital cortex, anterior and posterior cingulate cortices, and parietal cortex (p = 0.003-0.010). Voxel-based group comparison confirmed these differences. Amongst the PET-derived parameters, the Statistical Parametric Mapping-based whole brain β-amyloid load yielded the closest correlation with the Mini-Mental State Examination scores (r = -0.736, p < 0.001), following a nonlinear regression curve. No serious adverse events or other safety concerns were seen., Conclusion: These results indicate florbetaben to be a safe and efficacious β-amyloid-targeted tracer with favourable brain kinetics. Subjects with AD could be easily differentiated from HCs by both visual and quantitative assessment of the PET data. The operator-independent, voxel-based analysis yielded whole brain β-amyloid load which appeared valuable as a surrogate marker of disease severity.

The positron emission tomography in combination with CT in hybrid, cross-modality imaging systems (PET/CT) gains more and more importance as a part of the treatment-planning procedure in radiotherapy. Positron emission tomography (PET), as a integral part of nuclear medicine imaging and non-invasive imaging technique, offers the visualization and quantification of pre-selected tracer metabolism. In combination with the structural information from CT, this molecular imaging technique has great potential to support and improve the outcome of the treatment-planning procedure prior to radiotherapy. By the choice of the PET-Tracer, a variety of different metabolic processes can be visualized. First and foremost, this is the glucose metabolism of a tissue as well as for instance hypoxia or cell proliferation. This paper comprises the system characteristics of hybrid PET/CT systems. Acquisition and processing protocols are described in general and modifications to cope with the special needs in radiooncology. This starts with the different position of the patient on a special table top, continues with the use of the same fixation material as used for positioning of the patient in radiooncology while simulation and irradiation and leads to special processing protocols that include the delineation of the volumes that are subject to treatment planning and irradiation (PTV, GTV, CTV, etc.). General CT acquisition and processing parameters as well as the use of contrast enhancement of the CT are described. The possible risks and pitfalls the investigator could face during the hybrid-imaging procedure are explained and listed. The interdisciplinary use of different imaging modalities implies a increase of the volume of data created. These data need to be stored and communicated fast, safe and correct. Therefore, the DICOM-Standard provides objects and classes for this purpose (DICOM RT). Furthermore, the standard DICOM objects and classes for nuclear medicine (NM, PT) and computed tomography (CT) are used to communicate the actual image data created by the modalities. Care must be taken for data security, especially when transferring data across the (network-) borders of different hospitals. Overall, the most important precondition for successful integration of functional imaging in RT treatment planning is the goal orientated as well as close and thorough communication between nuclear medicine and radiotherapy departments on all levels of interaction (personnel, imaging protocols, GTV delineation, and selection of the data transfer method)., (Copyright 2010 European Society for Therapeutic Radiology and Oncology and European Association of Nuclear Medicine. Published by Elsevier Ireland Ltd.. All rights reserved.)