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The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.

PurposeTo investigate the performance of the new long axial field-of-view (LAFOV) Biograph Vision Quadra PET/CT and a standard axial field-of-view (SAFOV) Biograph Vision 600 PET/CT (both: Siemens Healthineers) system using an intra-patient comparison.MethodsForty-four patients undergoing routine oncological PET/CT were prospectively included and underwent a same-day dual-scanning protocol following a single administration of either 18F-FDG (n = 20), 18F-PSMA-1007 (n = 16) or 68Ga-DOTA-TOC (n = 8). Half the patients first received a clinically routine examination on the SAFOV (FOVaxial 26.3 cm) in continuous bed motion and then immediately afterwards on the LAFOV system (10-min acquisition in list mode, FOVaxial 106 cm); the second half underwent scanning in the reverse order. Comparisons between the LAFOV at different emulated scan times (by rebinning list mode data) and the SAFOV were made for target lesion integral activity, signal to noise (SNR), target lesion to background ratio (TBR) and visual image quality.ResultsEquivalent target lesion integral activity to the SAFOV acquisitions (16-min duration for a 106 cm FOV) were obtained on the LAFOV in 1.63 ± 0.19 min (mean ± standard error). Equivalent SNR was obtained by 1.82 ± 1.00 min LAFOV acquisitions. No statistically significant differences (p > 0.05) in TBR were observed even for 0.5 min LAFOV examinations. Subjective image quality rated by two physicians confirmed the 10 min LAFOV to be of the highest quality, with equivalence between the LAFOV and the SAFOV at 1.8 ± 0.85 min. By analogy, if the LAFOV scans were maintained at 10 min, proportional reductions in applied radiopharmaceutical could obtain equivalent lesion integral activity for activities under 40 MBq and equivalent doses for the PET component of <1 mSv.ConclusionImproved image quality, lesion quantification and SNR resulting from higher sensitivity were demonstrated for an LAFOV system in a head-to-head comparison under clinical conditions. The LAFOV system could deliver images of comparable quality and lesion quantification in under 2 min, compared to routine SAFOV acquisition (16 min for equivalent FOV coverage). Alternatively, the LAFOV system could allow for low-dose examination protocols. Shorter LAFOV acquisitions (0.5 min), while of lower visual quality and SNR, were of adequate quality with respect to target lesion identification, suggesting that ultra-fast or low-dose acquisitions can be acceptable in selected settings.

Molecular imaging has experienced enormous advancements in the areas of imaging technology, imaging probe and contrast development, and data quality, as well as machine learning-based data analysis. Positron emission tomography (PET) and its combination with computed tomography (CT) or magnetic resonance imaging (MRI) as a multimodality PET–CT or PET–MRI system offer a wealth of molecular, functional and morphological data with a single patient scan. Despite the recent technical advances and the availability of dozens of disease-specific contrast and imaging probes, only a few parameters, such as tumour size or the mean tracer uptake, are used for the evaluation of images in clinical practice. Multiparametric in vivo imaging data not only are highly quantitative but also can provide invaluable information about pathophysiology, receptor expression, metabolism, or morphological and functional features of tumours, such as pH, oxygenation or tissue density, as well as pharmacodynamic properties of drugs, to measure drug response with a contrast agent. It can further quantitatively map and spatially resolve the intertumoural and intratumoural heterogeneity, providing insights into tumour vulnerabilities for target-specific therapeutic interventions. Failure to exploit and integrate the full potential of such powerful imaging data may lead to a lost opportunity in which patients do not receive the best possible care. With the desire to implement personalized medicine in the cancer clinic, the full comprehensive diagnostic power of multiplexed imaging should be utilized.In this Review, Schwenck et al. discuss how PET imaging of cancer has advanced through its combination with CT and MRI and the development of an array of imaging probes, and how these innovations now need to be fully integrated into the clinic to improve cancer diagnostics and guide therapy.

PurposeDiverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results.MethodsGuidelines from related fields and relevant literature have been considered in consultation with leading experts involved in the management of PPGL. The provided information should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals.ConclusionSince the European Association of Nuclear Medicine 2012 guidelines, the excellent results obtained with gallium-68 (68Ga)-labelled somatostatin analogues (SSAs) in recent years have simplified the imaging approach for PPGL patients that can also be used for selecting patients for peptide receptor radionuclide therapy as a potential alternative or complement to the traditional theranostic approach with iodine-123 (123I)/iodine-131 (131I)-labelled meta-iodobenzylguanidine. Genomic characterisation of subgroups with differing risk of lesion development and subsequent metastatic spread is refining the use of molecular imaging in the personalised approach to hereditary PPGL patients for detection, staging, and follow-up surveillance.

RationaleThe development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions.MethodsA panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process.ResultsAccording to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET.ConclusionsThe E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.

PurposeThe lack of effective molecular biomarkers to monitor idiopathic pulmonary fibrosis (IPF) activity or treatment response remains an unmet clinical need. Herein, we determined the utility of fibroblast activation protein inhibitor for positron emission tomography (FAPI PET) imaging in a mouse model of pulmonary fibrosis.MethodsPulmonary fibrosis was induced by intratracheal administration of bleomycin (1 U/kg) while intratracheal saline was administered to control mice. Subgroups from each cohort (n = 3–5) underwent dynamic 1 h PET/CT after intravenously injecting FAPI-46 radiolabeled with gallium-68 ([68 Ga]Ga-FAPI-46) at 7 days and 14 days following disease induction. Animals were sacrificed following imaging for ex vivo gamma counting and histologic correlation. [68 Ga]Ga-FAPI-46 uptake was quantified and reported as percent injected activity per cc (%IA/cc) or percent injected activity (%IA). Lung CT density in Hounsfield units (HU) was also correlated with histologic examinations of lung fibrosis.ResultsCT only detected differences in the fibrotic response at 14 days post-bleomycin administration. [68 Ga]Ga-FAPI-46 lung uptake was significantly higher in the bleomycin group than in control subjects at 7 days and 14 days. Significantly (P = 0.0012) increased [68 Ga]Ga-FAPI-46 lung uptake in the bleomycin groups at 14 days (1.01 ± 0.12%IA/cc) vs. 7 days (0.33 ± 0.09%IA/cc) at 60 min post-injection of the tracer was observed. These findings were consistent with an increase in both fibrinogenesis and FAP expression as seen in histology.ConclusionCT was unable to assess disease activity in a murine model of IPF. Conversely, FAPI PET detected both the presence and activity of lung fibrogenesis, making it a promising tool for assessing early disease activity and evaluating the efficacy of therapeutic interventions in lung fibrosis patients.

PurposeThe advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, leading to a string of approvals in recent years. Herein, a narrative review on the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the ever-evolving treatment landscape of advanced NSCLC is presented.MethodsThis comprehensive review will begin with an introduction into current treatment paradigms incorporating ICIs; the evolution of CT-based criteria; moving onto novel phenomena observed with ICIs and the current state of hybrid imaging for diagnosis, treatment planning, evaluation of treatment efficacy and toxicity in advanced NSCLC, also taking into consideration its limitations and future directions.ConclusionsThe advent of ICIs marks the dawn of a new era bringing forth new challenges particularly vis-à-vis treatment response assessment and observation of novel phenomena accompanied by novel systemic side effects. While FDG PET/CT is widely adopted for tumor volume delineation in locally advanced disease, response assessment to immunotherapy based on current criteria is of high clinical value but has its inherent limitations. In recent years, modifications of established (PET)/CT criteria have been proposed to provide more refined approaches towards response evaluation. Not only a comprehensive inclusion of PET-based response criteria in prospective randomized controlled trials, but also a general harmonization within the variety of PET-based response criteria is pertinent to strengthen clinical implementation and widespread use of hybrid imaging for response assessment in NSCLC.

For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, we need to better understand the pathophysiological cascade of Aβ- and tau-related processes. Therefore, we set out to investigate how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer’s disease (AD) continuum. Using human cross-sectional and longitudinal neuroimaging and cognitive assessment data, we show that in early stages of AD, increased concentration of soluble CSF p-tau is strongly associated with accumulation of insoluble tau aggregates across the brain, and CSF p-tau levels mediate the effect of Aβ on tau aggregation. Further, higher soluble p-tau concentrations are mainly related to faster accumulation of tau aggregates in the regions with strong functional connectivity to individual tau epicenters. In this early stage, higher soluble p-tau concentrations is associated with cognitive decline, which is mediated by faster increase of tau aggregates. In contrast, in AD dementia, when Aβ fibrils and soluble p-tau levels have plateaued, cognitive decline is related to the accumulation rate of insoluble tau aggregates. Our data suggest that therapeutic approaches reducing soluble p-tau levels might be most favorable in early AD, before widespread insoluble tau aggregates. The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient’s guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as \"strict guidelines\" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards \"official\" guidelines on atherosclerosis imaging with PET.

Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma. To estimate the tracer PIF, we corrected an IDIF from the carotid artery with estimates of plasma parent fraction (PF) and plasma-to-whole blood (PWB) ratio obtained from five venous samples. We compared the combined IDIF+venous approach to gold standard data from arterial sampling in 10 healthy volunteers undergoing [18F]GE-179 brain PET imaging of the NMDA receptor. Arterial and venous PF and PWB ratio estimates determined from 7 patients with traumatic brain injury (TBI) were also compared to assess the potential effect of medication. There was high agreement between areas under the curves of the estimates of PF (r = 0.99, p<0.001), PWB ratio (r = 0.93, p<0.001), and the PIF (r = 0.92, p<0.001) as well as total distribution volume (VT) in 11 regions across the brain (r = 0.95, p<0.001). IDIF+venous VT had a mean bias of −1.7% and a comparable regional coefficient of variation (arterial: 21.3 ± 2.5%, IDIF+venous: 21.5 ± 2.0%). Simplification of the IDIF+venous method to use only one venous sample provided less accurate VT estimates (mean bias 9.9%; r = 0.71, p<0.001). A version of the method that avoids the need for blood sampling by combining the IDIF with population-based PF and PWB ratio estimates systematically underestimated VT (mean bias −20.9%), and produced VT estimates with a poor correlation to those obtained using arterial data (r = 0.45, p<0.001). Arterial and venous blood data from 7 TBI patients showed high correlations for PF (r = 0.92, p = 0.003) and PWB ratio (r = 0.93, p = 0.003). In conclusion, the IDIF+venous method with five venous samples provides a viable alternative to arterial sampling for quantification of [18F]GE-179 VT.