Use Of Positron Emission Tomography Imaging Research Articles

Positron Emission Tomography Imaging-based Analysis of Biological Functions

Positron emission tomography (PET) refers to a noninvasive imaging modality that enables ultrahigh-sensitivity quantitative evaluation of the spatiotemporal dynamics of targeted molecules within living organisms from outside the body. In this review, we explain the principles of PET imaging technology and the basic properties of ultrahigh sensitivity and quantifiability. Furthermore, we have outlined PET imaging-based integrated approaches to elucidate the fundamental neurobiological mechanisms underlying neuropsychiatric activity, as well as the usefulness of PET imaging in pharmacokinetic analysis and theranostics during drug development.

Positron Emission Tomography in Heart Failure: From Pathophysiology to Clinical Application.

Imaging modalities are increasingly being used to evaluate the underlying pathophysiology of heart failure. Positron emission tomography (PET) is a non-invasive imaging technique that uses radioactive tracers to visualize and measure biological processes in vivo. PET imaging of the heart uses different radiopharmaceuticals to provide information on myocardial metabolism, perfusion, inflammation, fibrosis, and sympathetic nervous system activity, which are all important contributors to the development and progression of heart failure. This narrative review provides an overview of the use of PET imaging in heart failure, highlighting the different PET tracers and modalities, and discussing fields of present and future clinical application.

Evaluated and recommended cross-section data for production of radionuclides with emerging interest in nuclear medicine imaging. Part 1: Positron emission tomography (PET)

Evaluated reactions for production of thirteen radionuclides with emerging interest for use in PET imaging are reported. Experimental cross section data for 53 possible production routes were compiled and discussed. A selection of sets was proposed for Padé fit leading to recommended values. Only routes for which at least two independent experimental studies were found, with data points over wider overlapping energy regions, were considered for selection and fitting. Padé fits for cross sections and their uncertainties are presented for production reactions of the positron emitters: 34mCl (1 route), 38K (1 route), 43Sc (2 routes), 45Ti (2 routes), 51Mn (2 routes), 61Cu (1 route), 69Ge (5 routes), 72As (1 route), 72Se (3 routes), 76Br-76Kr (1 route), 83Sr (2 routes), 86Zr (1 route), 152Tb (4 routes). Integral production yields on the basis of Padé fit recommended data are calculated. A comparison with results of TALYS-code calculations is made.

131 USE OF FDG-PET BRAIN IMAGING IN THE DIAGNOSIS AND MANAGEMENT OF DEMENTIA IN A UNIVERSITY HOSPITAL

Abstract Background Neuroimaging is an increasingly important tool dementia work-up. Subtype diagnosis helps predict the course of the disease, aiding prognostication and management. Amyloid-beta peptide is intrinsic to the pathogenesis of Alzheimer’s disease (AD), forming characteristic neuritic plaques which can be imaged in vivo on positron emission tomography (PET) scans. NICE recommendations advise use of PET imaging if dementia sub-type diagnosis is unclear and AD is suspected. We sought to establish the referral patterns for FDG-PET brain scans for patients aged 60 and over in a university hospital and to establish whether this imaging modality contributed to a change in diagnosis or treatment. Methods Requests for FDG-PET CT brain from 2019 – 2022 were retrospectively reviewed. Information was obtained from clinical notes and patient information software. Patient demographics, indication for scan, source of referral and whether imaging results led to a change in diagnosis or treatment was recorded. Results A total of 32 patients were reviewed, with a mean age of 65 years (13 females; 41%). We further analysed the 25 who were aged over 60; this subgroup had a mean age of 70 (9 females; 36%). All 25 patients were appropriately referred to assess for dementia subtype. A revision in diagnosis based on PET imaging was made in 17 (68%) cases. In 9 (30%) cases, results prompted change in dementia-specific pharmacological treatment, including donepezil and memantine. A further 6 (24%) had pharmacological treatment for non-cognitive symptoms of dementia adjusted, such as anti-depressants or anti-psychotics. The majority of referrals had come from neurologists (n = 15; 60%) rather than geriatricians (n = 10; 40%). The final diagnosis was AD in 12 cases (48%) and fronto-temporal dementia in 3 cases (12%). Conclusion PET scans are a useful functional imaging modality which can help to differentiate dementia subtypes and influence management.

Use of PET Imaging to Assess the Efficacy of Thiethylperazine to Stimulate Cerebral MRP1 Transport Activity in Wild-Type and APP/PS1-21 Mice.

Multidrug resistance-associated protein 1 (MRP1, encoded by the ABCC1 gene) may contribute to the clearance of amyloid-beta (Aβ) peptides from the brain into the blood and stimulation of MRP1 transport activity may be a therapeutic approach to enhance brain Aβ clearance. In this study, we assessed the effect of thiethylperazine, an antiemetic drug which was shown to stimulate MRP1 activity in vitro and to decrease Aβ load in a rapid β-amyloidosis mouse model (APP/PS1-21), on MRP1 transport activity by means of positron emission tomography (PET) imaging with the MRP1 tracer 6-bromo-7-[11C]methylpurine. Groups of wild-type, APP/PS1-21 and Abcc1(−/−) mice underwent PET scans before and after a 5-day oral treatment period with thiethylperazine (15 mg/kg, once daily). The elimination rate constant of radioactivity (kelim) was calculated from time–activity curves in the brain and the lungs as a measure of tissue MRP1 activity. Treatment with thiethylperazine had no significant effect on MRP1 activity in the brain and the lungs of wild-type and APP/PS1-21 mice. This may either be related to a lack of an MRP1-stimulating effect of thiethylperazine in vivo or to other factors, such as substrate-dependent MRP1 stimulation, insufficient target tissue exposure to thiethylperazine or limited sensitivity of the PET tracer to measure MRP1 stimulation.

A new automated and putatively versatile synthesis of the PSMA-ligand derivative [18F]DCFPyL using the FASTlabTM synthesizer

BackgroundNoninvasive molecular imaging using peptides and biomolecules labelled with positron emitters has become important for detection of cancer and other diseases with PET (positron emission tomography). The positron emitting radionuclide fluorine-18 is widely available in high yield from cyclotrons and has favorable decay (t1/2 109.7 min) and imaging properties. 18F-Labelling of biomolecules and peptides for use as radiotracers is customarily achieved in a two-step approach, which can be challenging to automate. 6-[18F]Fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([18F]F-Py-TFP) is a versatile 18F-prosthetic group for this purpose, which can be rapidly be produced in an one-step approach on solid support. This work details an automated procedure on the cassette-based GE FASTlab™ platform for the labeling of a peptidomimetic, exemplified by the case of using the Glu-CO-Lys motif to produce [18F]DCFPyL, a ligand targeting the prostate specific membrane antigen (PSMA).ResultsFrom fluorine-18 delivery a fully automated two-step radiosynthesis of [18F]DCFPyL was completed in 56 min with an overall end of synthesis yield as high as 37% using solid phase extraction (SPE) purification on the GE FASTlab™ platform.ConclusionsPutatively, this radiolabeling methodology is inherently amenable to automation with a diverse set of synthesis modules, and it should generalize for production of a broad spectrum of biomolecule-based radiotracers for use in PET imaging.

Neutral Ligands as Potential 64Cu Chelators for Positron Emission Tomography Imaging Applications in Alzheimer's Disease.

Positron emission tomography (PET), which uses positron-emitting radionuclides to visualize and measure processes in the human body, is a useful noninvasive diagnostic tool for Alzheimer's disease (AD). The development of longer-lived radiolabeled compounds is essential for further expansion of the use of PET imaging in healthcare, and diagnostic agents employing longer-lived radionuclides such as 64Cu (t1/2 = 12.7 h, β+ = 17%, β- = 39%, electron capture EC = 43%, and Emax = 0.656 MeV) can accomplish this task. One limitation of 64Cu PET agents for neuroimaging applications is their limited lipophilicity due to the presence of several anionic groups needed to ensure strong Cu chelation. Herein, we evaluate a series of neutral chelators containing the 1,4,7-triazacyclononane or 2,11-diaza[3.3](2,6)pyridinophane macrocycles that have pyridyl-containing arms incorporating Aβ-peptide-interacting fragments. The crystal structures of the corresponding Cu complexes confirm that the pyridyl N atoms are involved in binding to Cu. Radiolabeling and autoradiography studies show that the compounds efficiently chelate 64Cu, and the resulting complexes exhibit specific binding to the amyloid plaques in the AD mouse brain sections versus wild-type controls.

60 Years of Achievements by KSNM in Neuroimaging Research.

Nuclear medicine neuroimaging is able to show functional and molecular biologic abnormalities in various neuropsychiatric diseases. Therefore, it has played important roles in the clinical diagnosis and in research on the normal and pathological states of the brain. More than 400 outstanding studies have been conducted by Korean researchers over the past 60years. In the 1990s, when multiheaded single-photon emission computed tomography (SPECT) scanners were first introduced in South Korea, stroke research using brain perfusion SPECT was conducted. With the spread of positron emission tomography (PET) scanners in the 2000s, research on the clinical usefulness of PET and the evaluation of pathophysiology in various diseases such as epilepsy, brain tumors, degenerative brain diseases, and other neuropsychiatric diseases were actively conducted using [18F]FDG and various neuroreceptor tracers. In the 2010s, with the clinical application of new radiopharmaceuticals for amyloid and tau imaging, research demonstrating the clinical usefulness of PET imaging and the pathophysiology of dementia has increased rapidly. It is expected that the role of nuclear medicine will expand with the development of new radiopharmaceuticals and analysis technologies, along with the application of artificial intelligence for early and differential diagnosis, and the development of therapeutic agents for degenerative brain diseases.

Use of PET Imaging in Neuro-Oncological Surgery.

Simple SummaryThe use of positron emission tomography (PET) imaging in neuro-oncological surgery is an exciting field with thriving perspectives. Increasing evidence exists for amino acid-based PET to facilitate interpretation of imaging findings following therapeutic interventions in patients with glioma and brain metastases. In meningioma patients, radiolabeled somatostatin receptor ligands provide an improved tumor tissue visualization in lesions located in the vicinity of the skull base and differentiate between scar tissue and tumor recurrence. Moreover, they can be applied as an individual treatment option in recurrent atypical and anaplastic meningioma not eligible for further surgery and radiotherapy. With a focus on its clinical application, this review provides an overview of the emerging field of PET imaging in neuro-oncological surgery.This review provides an overview of current applications and perspectives of PET imaging in neuro-oncological surgery. The past and future of PET imaging in the management of patients with glioma and brain metastases are elucidated with an emphasis on amino acid tracers, such as O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET). The thematic scope includes surgical resection planning, prognostication, non-invasive prediction of molecular tumor characteristics, depiction of intratumoral heterogeneity, response assessment, differentiation between tumor progression and treatment-related changes, and emerging new tracers. Furthermore, the role of PET using specific somatostatin receptor ligands for the management of patients with meningioma is discussed. Further advances in neuro-oncological imaging can be expected from promising new techniques, such as hybrid PET/MR scanners and the implementation of artificial intelligence methods, such as radiomics.

Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients - a report of the PET/RANO group.

The management of patients with glioma usually requires multimodality treatment including surgery, radiotherapy, and systemic therapy. Accurate neuroimaging plays a central role for radiotherapy planning and follow-up after radiotherapy completion. In order to maximize the radiation dose to the tumor and to minimize toxic effects on the surrounding brain parenchyma, reliable identification of tumor extent and target volume delineation is crucial. The use of positron emission tomography (PET) for radiotherapy planning and monitoring in gliomas has gained considerable interest over the last several years, but Class I data are not yet available. Furthermore, PET has been used after radiotherapy for response assessment and to distinguish tumor progression from pseudoprogression or radiation necrosis. Here, the Response Assessment in Neuro-Oncology (RANO) working group provides a summary of the literature and recommendations for the use of PET imaging for radiotherapy of patients with glioma based on published studies, constituting levels 1-3 evidence according to the Oxford Centre for Evidence-based Medicine.

Breast Cancer and PET Imaging.

Breast cancer is the most common malignancy in women and among the most common indications of oncologic positron emission tomography (PET) studies. In this review article, updated anatomical, pathological, and clinical information about breast cancer were provided for Nuclear Medicine physicians to better understand breast cancer and interpret PET images and a review of the literature on the use of PET imaging in breast cancer was summarized.

Longitudinal evaluation of a novel BChE PET tracer as an early in vivo biomarker in the brain of a mouse model for Alzheimer disease.

Purpose: The increase in butyrylcholinesterase (BChE) activity in the brain of Alzheimer disease (AD) patients and animal models of AD position this enzyme as a potential biomarker of the disease. However, the information on the ability of BChE to serve as AD biomarker is contradicting, also due to scarce longitudinal studies of BChE activity abundance. Here, we report 11C-labeling, in vivo stability, biodistribution, and longitudinal study on BChE abundance in the brains of control and 5xFAD (AD model) animals, using a potent BChE selective inhibitor, [11C]4, and positron emission tomography (PET) in combination with computerised tomography (CT). We correlate the results with in vivo amyloid beta (Aβ) deposition, longitudinally assessed by [18F]florbetaben-PET imaging.Methods: [11C]4 was radiolabelled through 11C-methylation. Metabolism studies were performed on blood and brain samples of female wild type (WT) mice. Biodistribution studies were performed in female WT mice using dynamic PET-CT imaging. Specific binding was demonstrated by ex vivo and in vivo PET imaging blocking studies in female WT and 5xFAD mice at the age of 7 months. Longitudinal PET imaging of BChE was conducted in female 5xFAD mice at 4, 6, 8, 10 and 12 months of age and compared to age-matched control animals. Additionally, Aβ plaque distribution was assessed in the same mice using [18F]florbetaben at the ages of 2, 5, 7 and 11 months. The results were validated by ex vivo staining of BChE at 4, 8, and 12 months and Aβ at 12 months on brain samples.Results: [11C]4 was produced in sufficient radiochemical yield and molar activity for the use in PET imaging. Metabolism and biodistribution studies confirmed sufficient stability in vivo, the ability of [11C]4 to cross the blood brain barrier (BBB) and rapid washout from the brain. Blocking studies confirmed specificity of the binding. Longitudinal PET studies showed increased levels of BChE in the cerebral cortex, hippocampus, striatum, thalamus, cerebellum and brain stem in aged AD mice compared to WT littermates. [18F]Florbetaben-PET imaging showed similar trend of Aβ plaques accumulation in the cerebral cortex and the hippocampus of AD animals as the one observed for BChE at ages 4 to 8 months. Contrarily to the results obtained by ex vivo staining, lower abundance of BChE was observed in vivo at 10 and 12 months than at 8 months of age.Conclusions: The BChE inhibitor [11C]4 crosses the BBB and is quickly washed out of the brain of WT mice. Comparison between AD and WT mice shows accumulation of the radiotracer in the AD-affected areas of the brain over time during the early disease progression. The results correspond well with Aβ accumulation, suggesting that BChE is a promising early biomarker for incipient AD.

Novel PET Biomarkers to Disentangle Molecular Pathways across Age-Related Neurodegenerative Diseases.

There is a need to disentangle the etiological puzzle of age-related neurodegenerative diseases, whose clinical phenotypes arise from known, and as yet unknown, pathways that can act distinctly or in concert. Enhanced sub-phenotyping and the identification of in vivo biomarker-driven signature profiles could improve the stratification of patients into clinical trials and, potentially, help to drive the treatment landscape towards the precision medicine paradigm. The rapidly growing field of neuroimaging offers valuable tools to investigate disease pathophysiology and molecular pathways in humans, with the potential to capture the whole disease course starting from preclinical stages. Positron emission tomography (PET) combines the advantages of a versatile imaging technique with the ability to quantify, to nanomolar sensitivity, molecular targets in vivo. This review will discuss current research and available imaging biomarkers evaluating dysregulation of the main molecular pathways across age-related neurodegenerative diseases. The molecular pathways focused on in this review involve mitochondrial dysfunction and energy dysregulation; neuroinflammation; protein misfolding; aggregation and the concepts of pathobiology, synaptic dysfunction, neurotransmitter dysregulation and dysfunction of the glymphatic system. The use of PET imaging to dissect these molecular pathways and the potential to aid sub-phenotyping will be discussed, with a focus on novel PET biomarkers.

Advanced Quantitative MSK Imaging.

For many years, imaging of the musculoskeletal (MSK) system has focused on subjective and qualitative analysis. However, quantitative assessment of imaging data may provide precise and reproducible image-derived metrics, and through their use there is a promise of increased value of imaging. Specifically, these metrics, or biomarkers, may be used for improved diagnosis, determination of patient prognosis, and monitoring of treatment response. This issue of Seminars in Musculoskeletal Radiology is dedicated to quantitative MSK imaging. Giraudo et al provide a comprehensive overview of the quantitative methods that can be applied to assess inflammatory rheumatologic diseases, considering not only different radiologic techniques but also hybrid imaging. In addition, they describe emerging technologies such as artificial intelligence and radiomics. Burge and Jawetz discuss advanced magnetic resonance imaging (MRI) techniques in osteoarthritis that can comprehensively evaluate joint health, providing additional information regarding both cartilage status and the state of surrounding articular tissues. Gitto and colleagues discuss the currently available state-of-the-art quantitative ultrasound imaging tools available in MSK radiology including shear-wave elastography, perfusion with contrast-enhanced ultrasound and superb microvascular imaging, and quantitative ultrasound assessment of osteosarcopenia. Hemke et al present an overview of quantitative imaging methods to assess the distribution of lean tissue, adipose tissue, and bone in the human body, and their relationship with various pathologies. They stress the importance of body composition imaging for predicting overall health and risk profiling of patients. Jerban and colleagues summarize the quantitative MRI techniques recently developed for cortical and trabecular bone evaluation. Compared with radiograph-based techniques that focus on measuring bone mineral density, the new quantitative MRI techniques can comprehensively evaluate all the components of bone including the organic matrix, bone minerals, water, and fat. Weber et al review the role of neuromuscular imaging in the diagnosis of inherited and acquired muscle diseases. They discuss whole-body imaging as well as more advanced MRI applications including nonproton MRI and multiparametric quantitative imaging that provides deeper insights into muscle pathophysiology. Griffith describes the role of quantitative imaging for the assessment of spine abnormalities. These quantitative techniques have led to a greater understanding of spinal development, marrow physiology, and disease pathogenesis. In their article on quantitative musculoskeletal tumor imaging, Howe and colleagues highlight the emerging role of various quantitative MRI and positron emission tomography (PET) techniques for the characterization, staging, prognosis, and follow-up of bone and soft tissue tumors. They also touch on the role of computed tomography and MRI-based virtual surgical planning and three-dimensional printing as a means to optimize surgical treatment of MSK tumors. Yoon et al review novel approaches to pinpoint MSK pain generators with the use of PET imaging. They also discuss the added value of new radiotracers and of combining information in one hybrid PET/MRI examination. Liu presents the concepts of deep learning and demonstrates how these methods applied to quantitative MRI may accelerate image acquisition and reconstruction, improve tissue segmentation, and aid in the detection of structural knee abnormalities. Finally, Visser and colleagues discuss the trend in medicine that is moving from volume- to value-based payments, and they review the role that quantitative imaging may play. They also discuss the influence of artificial intelligence on value-based health care. The variety of applications across all imaging modalities presented in this issue exemplifies the significant effort being made in developing and validating quantitative imaging techniques applied to the MSK system. The fact that several novel applications are still at the stage of development and optimization while other, more established, methods are already being translated into the clinical applications, demonstrates the tremendous ongoing activity in the field of quantitative MSK imaging. We thank all the authors for their outstanding contribution to this issue. We hope the readers will be as excited as we are to apply quantitative imaging biomarkers in their clinical practice.

Positron Emission Tomography to Evaluate Response in the Cervix and Lymph Nodes after Definitive Chemoradiation and Immunotherapy for Cervical Cancer Patients Treated on GOG 9929

Positron emission tomography (PET) has been shown to be prognostic for response and survival after standard chemoradiation (CRT) for cervical cancer. We investigated the role of PET in evaluating the primary tumor and metastatic lymph nodes after CRT and immunotherapy for locally advanced cervical cancer (LACC) patients (pts) treated with standard chemoradiation (CRT) followed by ipilimumab on GOG 9929. Node positive LACC pts were prospectively enrolled and treated with 6 weekly doses of cisplatin (40 mg/m2) and extended field radiation therapy. A pretreatment PET scan was required. Two to 6 weeks after CRT completion, pts with no evidence of disease progression initiated ipilimumab once every 3 weeks for 4 planned doses. Two dose levels were evaluated: 3mg/kg (DL1) and 10mg/kg (DL2), with an expansion at 10mg/kg. Pts had a post ipilimumab PET scan at 4-12 weeks. Further investigation of the cervix pre and post therapy PET scan used two metrics: (a) standardized uptake value (SUV), and (b) ratio of post-therapy SUVmax: pre-therapy SUVmax. We then correlated the PET response with 1-year disease free and overall survival data. All radiation plans underwent RT quality review with a radiation oncologist specializing in gynecology oncology. Thirty-two of 34 enrolled pts initiated study treatment, of whom 18 pts have complete pre and post therapy PET data, with at least 1 dose of ipilimumab. Of the 18 pts, 89% were squamous histology; all had positive pelvic lymph nodes (PVLN), and 47% had positive para-aortic lymph nodes (PALN). All pts completed CRT, with ipilimumab completion rates of 72% with 4 cycles, 11% with 3 cycles, 11% with 2 cycles and 6% with 1 cycle. There were no minor or major RT quality deviations. 18 patients have a measure of post ipilimumab PET scan response for the cervix: 13 had a complete response (CR), three had a partial response (PR), and two had stable disease (SD). 17 patients have a measure of PET scan response for PVLN: 8 had a CR, 7 had a PR, and 2 had SD. 3 patients have a measure of PET scan response for PALN, and all had a CR. In the 18 patients, the 12-month OS is 94% and the 12-month RFS is 88%. In the 18 patients, there were 2 recurrences, one of whom died: one had a CR in both cervix and PVLN, with no PALN data; the pt who recurred and died had a CR in cervix and a PR in PVLN, with no PALN data. This study is the first to describe the use of PET imaging as a prognostic imaging biomarker for cervical cancer after CRT and immunotherapy. Our data suggests that the post therapy PET could be used as an early correlate of response, and a potential biomarker tool for clinical trials and practice in cervical cancer.

Synthesis and Automated Labeling of [18F]Darapladib, a Lp-PLA2 Ligand, as Potential PET Imaging Tool of Atherosclerosis.

Atherosclerosis and its associated clinical complications are major health issues in industrialized countries. Lipoprotein-associated phospholipase A2 (Lp-PLA2) was demonstrated to play an important role in atherogenesis and to be a potential risk prediction factor of plaque rupture. Darapladib is one of the most potent Lp-PLA2 inhibitors with an IC50 of 0.25 nM. Using its affinity for Lp-PLA2, we describe herein the total synthesis of darapladib radiolabeling precursor and the automated radiolabeling process for positron emission tomography (PET) imaging via an arylboronate moiety. The tracer thus obtained was tested in a mouse model of atherosclerosis (ApoE KO) and compared with the widely used [18F]fluorodeoxyglucose ([18F]FDG) PET tracer, known to label metabolically active cells. [18F]Darapladib showed a significant accumulation within mice aortic atheromatous plaques dissected out ex vivo compared to [18F]FDG. Incubation of the radiotracer with human carotid samples showed a strong accumulation within the atherosclerotic plaques and supports its potential for use in PET imaging.

ADVANCES IN THE MOLECULAR IMAGING OF ALZHEIMER'S DISEASE: NEUROBIOLOGICAL MECHANISMS OF DISEASE AND NEUROPSYCHIATRIC SYMPTOMS: Session 209

The pathogenesis of Alzheimer's disease (AD) remains elusive. The observed accumulations of beta amyloid and phosphorylated tau protein aggregates are thought to play key roles in initiating or propagating the disease. However, other processes including changes in synaptic proteins, neurotransmitter loss, inflammation and cerebrovascular disease have been suggested as important etiologies as well. Importantly, the recent, unprecedented advancements of positron emission tomography (PET) radiotracer chemistry allow investigations into molecular changes associated with AD. Until recently, much of what is known about AD pathology has been learned from post mortem studies and animal models. The advancements of PET imaging allows quantitative in vivo measurements of specific proteins within many brain regions. Because the manifestations of AD are heterogeneous. The use of PET imaging can be used to improve the understanding of diverse symptoms. For example, a majority of individuals experience neuropsychiatric symptoms during the disease process, but the onset and composition of these symptoms vary widely. Molecular imaging using PET allows us to study neurobiological processes both early in the disease process and longitudinally. PET imaging can be used in concert with other imaging modalities such as MRI, as well as assessments of cognition and neuropsychiatric symptoms to investigate the molecular underpinnings of AD. It is of great importance for clinicians to learn about these innovative and translational tools which will ultimately lead to the identification of disease biomarkers and therapeutic targets. The goal of this session is to illustrate the importance of in vivo molecular imaging in the study of AD with a specific emphasis on PET. Dr. Adam Mecca (Chair) will present results of cross-sectional studies that investigate synaptic protein alterations in individuals with AD. These investigations utilize specific PET tracers to quantify synaptic density and metabotrophic glutamate receptor subtype 5 (mGluR5). Dr. Nancy Donovan will describe research that examines the relationships between cortical and subcortical brain amyloid quantified using PET, anxiety, and AD risk in cognitively normal older adults. Dr. Jennifer Gatchel will present work on the association between depressive symptoms and in vivo cerebral tau and amyloid measurements. Dr. Gwenn Smith will describe the role of serotonin (5-HT), tau and amyloid b in cognitive decline in individuals with mild cognitive impairment and normal cognition. Finally, Dr. Donovan (Discussant) will lead the speakers in a panel discussion, along with Q&A involving session attendees.

PET imaging in patients with brain metastasis-report of the RANO/PET group.

Brain metastases (BM) from extracranial cancer are associated with significant morbidity and mortality. Effective local treatment options are stereotactic radiotherapy, including radiosurgery or fractionated external beam radiotherapy, and surgical resection. The use of systemic treatment for intracranial disease control also is improving. BM diagnosis, treatment planning, and follow-up is most often based on contrast-enhanced magnetic resonance imaging (MRI). However, anatomic imaging modalities including standard MRI have limitations in accurately characterizing posttherapeutic reactive changes and treatment response. Molecular imaging techniques such as positron emission tomography (PET) characterize specific metabolic and cellular features of metastases, potentially providing clinically relevant information supplementing anatomic MRI. Here, the Response Assessment in Neuro-Oncology working group provides recommendations for the use of PET imaging in the clinical management of patients with BM based on evidence from studies validated by histology and/or clinical outcome.

18F-FDG-PET and MRI in autoimmune encephalitis: a systematic review of brain findings

In the diagnostic assessment of autoimmune encephalitis (AE) associated with antineural antibody (Ab) imaging with 18F-fluorodeoxyglucose (FDG), positron emission tomography (PET) was initially only used to screen for occult malignancies in paraneoplastic cases. Today accumulating evidence also supports the use of PET imaging for the objective assessment of metabolic changes in the brain of patients with AE. On the other hand, magnetic resonance imaging (MRI) of the brain reveals a variable picture depending on the specific syndrome and associated antibody, and may be normal in a sizable proportion of patients. Among all the articles retrieved, we selected only studies and case series describing 18F-PET/CT, or multimodal imaging assessments (with both PET/CT and MRI performed in the same patient) on at least five patients with AE confirmed by the presence of antineural Ab. Studies describing MRI but not PET/CT findings on at least 20 cases were also included to strengthen the morphological considerations. We summarize the findings in the literature, commenting on studies involving the use of FDG-PET/CT in patients with AE, focusing on the added value and unsolved issues of using FDG-PET as opposed to MRI, and discussing them in the context of the available diagnostic criteria for AE. We also describe neuroimaging (PET and MRI) differences between AE with Ab against surface antigens vs AE with Ab against intracellular antigens. The timing of neuroimaging after the onset of symptoms is also considered. From a systematic review of the literature, it seems that some specific metabolic patterns correlate with the presence of specific Ab, such as a cerebral posterior hypometabolism in anti-NMDAR encephalitis, and a mesiotemporal hypermetabolism (associated with hyperintensities and swollen structures on MRI T2) in encephalitis with LGI1 and onconeural Ab. To ascertain the prognostic value of FDG-PET and its role in driving therapy, larger (preferably longitudinal) studies are needed on age-matched, untreated patients with the same Ab status, who undergo imaging at a similar time after the onset of their symptoms. This would enable a systematic correlation between MRI and FDG-PET findings, and help to clarify a number of unsolved clinical and technical issues.

Sex steroid hormones and brain function: PET imaging as a tool for research.

Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone‐mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression. Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, non‐invasive techniques are needed. Positron emission tomography (PET) is a non‐invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients.