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Cardiac amyloidosis includes a group of protein-misfolding diseases characterized by fibril accumulation within the extracellular space of the myocardium and cardiac dysfunction. Cardiac amyloidosis has high mortality. Emerging radionuclide techniques have helped us to better understand disease pathogenesis, prognostication, and treatment response in cardiac amyloidosis. PURPOSE OF REVIEW: To review recent advances in molecular imaging of cardiac amyloidosis using amyloid PET radiotracers. RECENT FINDINGS: Multiple single center studies have shown that amyloid PET radiotracers allow definitive diagnosis and quantification of cardiac amyloid burden. These amyloid targeting tracers may provide means to improve early disease detection, risk stratification and treatment monitoring. Amyloid PET imaging may inform definitive imaging-based diagnosis for therapeutic decisions, risk stratification, and treatment monitoring. More research in unselected cohorts of patients with suspected cardiac amyloidosis is needed to optimize the clinical implementation of amyloid PET imaging., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A key focus of cardiovascular medicine is the detection, treatment, and prevention of disease, with a move towards more personalized and patient-centred treatments. To achieve this goal, novel imaging approaches that allow for early and accurate detection of disease and risk stratification are needed. At present, the diagnosis, monitoring, and prognostication of thrombotic cardiovascular diseases are based on imaging techniques that measure changes in structural anatomy and biological function. Molecular imaging is emerging as a new tool for the non-invasive detection of biological processes, such as thrombosis, that can improve identification of these events above and beyond current imaging modalities. At the forefront of these evolving techniques is the use of high-sensitivity radiotracers in conjunction with positron emission tomography imaging that could revolutionise current diagnostic paradigms by improving our understanding of the role and origin of thrombosis in a range of cardiovascular diseases., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Introduction: Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application., Methods: We included 533 participants from AMYloid imaging to Prevent Alzheimer's Disease (AMYPAD DPMS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts. Thirty-two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces. Generalized estimating equations stratified by amyloid positivity were used to assess the impact of the quantification pipeline, radiotracer, age, brain atrophy, and harmonization status on CL., Results: RR selection and RR type impact CL the most, particularly in amyloid-negative individuals. The standard CL pipeline with the whole cerebellum as RR is robust against brain atrophy and differences in image resolution, with 95% confidence intervals below ± 3.95 CL for amyloid beta positivity cutoffs (CL < 24)., Discussion: The standard CL pipeline is recommended for most scenarios. Confidence intervals should be considered when operationalizing CL cutoffs in clinical and research settings., Highlights: We developed a framework for evaluating Centiloid (CL) variability to different factors. Reference region selection and delineation had the highest impact on CL values. Whole cerebellum (WCB) and whole cerebellum plus brainstem (WCB+BSTM) as reference regions yielded consistent results across tracers. The standard CL pipeline is robust against atrophy and image resolution variation. Estimated within- and between-pipeline variability (95% confidence interval) in absolute CL units., (© None The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Positron emission tomography imaging of misfolded proteins with high-affinity and selective radioligands has played a vital role in expanding our knowledge of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. The pathogenesis of Huntington's disease, a CAG trinucleotide repeat disorder, is similarly linked to the presence of protein fibrils formed from mutant huntingtin (mHTT) protein. Development of mHTT fibril-specific radioligands has been limited by the lack of structural knowledge around mHTT and a dearth of available hit compounds for medicinal chemistry refinement. Over the past decade, the CHDI Foundation, a non-for-profit scientific management organisation has orchestrated a large-scale screen of small molecules to identify high affinity ligands of mHTT, with lead compounds now reaching clinical maturity. Here we describe the mHTT radioligands developed to date and opportunities for further improvement of this radiotracer class., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Background: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool., Patients and Methods: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11 C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) ( 18 F-FACBC), or Gallium-68-prostate-specific-membrane-antigen ( 68 Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809)., Results: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68 Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68 Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68 Ga-PSMA and 18 F-FACBC parameters and for major maximum standardized uptake value at the first 11 C-Choline PET scan., Conclusions: Our study highlighted that 11 C-Choline, 68 Ga-PSMA, and 18 F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68 Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA., Competing Interests: Disclosure FM has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD, and Pfizer outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitor therapy targeting the PD-1/PD-L1 axis in cancer patients, is a promising oncological treatment. However, the number of non-responders remains high, causing a burden for the patient and the healthcare system. Consequently, a diagnostic tool to predict treatment outcomes would help with patient stratification. Molecular imaging provides said diagnostic tool by offering a whole-body quantitative assessment of PD-L1 expression, hence supporting therapy decisions. Four PD-L1 radioligand candidates containing a linker-chelator system for radiometalation, along with three hydrophilizing units-one sulfonic and two phosphonic acids-were synthesized. After labeling with 64 Cu, log D 7.4 values of less than -3.03 were determined and proteolytic stability confirmed over 94% intact compound after 48 h. Binding affinity was determined using two different assays, revealing high affinities up to 13 nM. µPET/CT imaging was performed in tumor-bearing mice to investigate PD-L1-specific tumor uptake and the pharmacokinetic profile of radioligands. These results yielded an unexpected in vivo distribution, such as low tumor uptake in PD-L1 positive tumors, high liver uptake, and accumulation in bone/bone marrow and potentially synovial spaces. These effects are likely caused by Ca 2+ -affinity and/or binding to macrophages. Despite phosphonic acids providing high water solubility, their incorporation must be carefully considered to avoid compromising the pharmacokinetic behavior of radioligands.

The excellent features of non-invasive molecular imaging, its progressive technology (real-time, whole-body imaging and quantification), and global impact by a growing infrastructure for positron emission tomography (PET) scanners are encouraging prospects to investigate new concepts, which could transform clinical care of complex infectious diseases. Researchers are aiming towards the extension beyond the routinely available radiopharmaceuticals and are looking for more effective tools that interact directly with causative pathogens. We reviewed and critically evaluated (challenges or pitfalls) antibiotic-derived PET radiopharmaceutical development efforts aimed at infection imaging. We considered both radiotracer development for infection imaging and radio-antibiotic PET imaging supplementing other tools for pharmacologic drug characterization; overall, a total of 20 original PET radiotracers derived from eleven approved antibiotics., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

In oncology, biomarker research aimed to provide insights on cancer biology via positron emission tomography (PET) and single photon emission tomography (SPECT) imaging has seen an incredible growth in the past two decades. Despite the increased number of publications on PET/SPECT radiopharmaceuticals, the field lacked standardization of in vitro and in vivo parameters necessary for the characterization of any radiotracer. Through the efforts of the World Molecular Imaging Society Education Committee, this white paper lays down validation studies that are essential to chemically and biologically characterize new radiopharmaceuticals derived from small molecules, peptides or proteins. Finally, a brief overview of the steps toward translation is also presented.Herein, we discuss the following: Chemistry and radiochemistry metrics to establish the identity of the imaging agent. In vitro and in vivo studies to examine the radiotracer's mechanism of action, which includes target specificity, pharmacokinetics and in vivo metabolism., (© 2021. The Author(s).)

Tumorigenesis is a multistep process marked by variations in numerous metabolic pathways that affect cellular architectures and functions. Cancer cells reprogram their energy metabolism to enable several basic molecular functions, including membrane biosynthesis, receptor regulations, bioenergetics, and redox stress. In recent years, cancer diagnosis and treatment strategies have targeted these specific metabolic changes and the tumor's interactions with its microenvironment. Positron emission tomography (PET) captures all molecular alterations leading to abnormal function and cancer progression. As a result, the development of PET radiotracers increasingly focuses on irregular biological pathways or cells that overexpress receptors that have the potential to function as biomarkers for early diagnosis and treatment measurements as well as research. This chapter reviews both established and evolving PET radiotracers used to image tumor biology. We have also included a few advantages and disadvantages of the routinely used PET radiotracers in cancer imaging., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI., Methods: The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m 2 ; and (3) diabetic patients. This trial's design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA., Conclusions: This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD., Trial Registration Number: NCT03354273.

There are two important topics in the field of cancer research: one is targeted molecular therapy and the other is tumor molecular imaging. Focal adhesion kinase (FAK) is considered as an attractive target for oncologic diagnosis and therapy. A series of 2,4-diaminopyrimidine derivatives were labeled with 18 F to study their biological properties and their potential as positron emission tomography tumor imaging agents. They inhibited the activity of FAK with IC 50 values in the wide range of 0.6-2164 nM, among which the IC 50 of Q6 was 3.2 nM. For the biodistribution in S180-bearing mice, the corresponding [ 18 F]Q6 was relatively good, with the highest uptake of 3.35 ± 0.32 % ID/g at 30 min postinjection, with a tumor/muscle ratio of 2.08 and a tumor/bone ratio of 2.48. Accordingly, [ 18 F]Q6 was considered as a potential PET imaging agent for tumor diagnosis.

Reactive astrocytes play a key role in the pathogenesis of various neurodegenerative diseases. Monoamine oxidase-B (MAO-B) is one of the promising targets for the imaging of astrogliosis in the human brain. A novel selective and reversible MAO-B tracer, ( S )-(2-methylpyrid-5-yl)-6-[(3- 18 F-fluoro-2-hydroxy)propoxy]quinoline ( 18 F-SMBT-1), was successfully developed via lead optimization from the first-generation tau PET tracer 18 F-THK-5351. Methods: SMBT-1 was radiolabeled with 18 F using the corresponding precursor. The binding affinity of radiolabeled compounds to MAO-B was assessed using saturation and competitive binding assays. The binding selectivity of 18 F-SMBT-1 to MAO-B was evaluated by autoradiography of frozen human brain tissues. The pharmacokinetics and metabolism were assessed in normal mice after intravenous administration of 18 F-SMBT-1. A 14-d toxicity study after the intravenous administration of 18 F-SMBT-1 was performed using rats and mice. Results: In vitro binding assays demonstrated a high binding affinity of 18 F-SMBT-1 to MAO-B (dissociation constant, 3.7 nM). In contrast, it showed low binding affinity to MAO-A and protein aggregates such as amyloid-β and tau fibrils. Autoradiographic analysis showed higher amounts of 18 F-SMBT-1 binding in the Alzheimer disease brain sections than in the control brain sections. 18 F-SMBT-1 binding was completely displaced with the reversible MAO-B inhibitor lazabemide, demonstrating the high selectivity of 18 F-SMBT-1 for MAO-B. Furthermore, 18 F-SMBT-1 showed a high uptake by brain, rapid washout, and no radiolabeled metabolites in the brain of normal mice. 18 F-SMBT-1 showed no significant binding to various receptors, ion channels, or transporters, and no toxic effects related to its administration were observed in mice and rats. Conclusion: 18 F-SMBT-1 is a promising and selective MAO-B PET tracer candidate, which would be useful for quantitative monitoring of astrogliosis in the human brain., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Target-specific biomolecules, monoclonal antibodies (mAb), proteins, and protein fragments are known to have high specificity and affinity for receptors associated with tumors and other pathological conditions. However, the large biomolecules have relatively intermediate to long circulation half-lives (>day) and tumor localization times. Combining superior target specificity of mAbs and high sensitivity and resolution of the PET (Positron Emission Tomography) imaging technique has created a paradigm-shifting imaging modality, ImmunoPET. In addition to metallic PET radionuclides, 124 I is an attractive radionuclide for radiolabeling of mAbs as potential immunoPET imaging pharmaceuticals due to its physical properties (decay characteristics and half-life), easy and routine production by cyclotrons, and well-established methodologies for radioiodination. The objective of this report is to provide a comprehensive review of the physical properties of iodine and iodine radionuclides, production processes of 124 I, various 124 I-labeling methodologies for large biomolecules, mAbs, and the development of 124 I-labeled immunoPET imaging pharmaceuticals for various cancer targets in preclinical and clinical environments. A summary of several production processes, including 123 Te(d,n) 124 I, 124 Te(d,2n) 124 I, 121 Sb(α,n) 124 I, 123 Sb(α,3n) 124 I, 123 Sb( 3 He,2n) 124 I, nat Sb(α, xn) 124 I, nat Sb( 3 He,n) 124 I reactions, a detailed overview of the 124 Te(p,n) 124 I reaction (including target selection, preparation, processing, and recovery of 124 I), and a fully automated process that can be scaled up for GMP (Good Manufacturing Practices) production of large quantities of 124 I is provided. Direct, using inorganic and organic oxidizing agents and enzyme catalysis, and indirect, using prosthetic groups, 124 I-labeling techniques have been discussed. Significant research has been conducted, in more than the last two decades, in the development of 124 I-labeled immunoPET imaging pharmaceuticals for target-specific cancer detection. Details of preclinical and clinical evaluations of the potential 124 I-labeled immunoPET imaging pharmaceuticals are described here., Competing Interests: The authors declare no conflict of interest.

Purpose of Review: Pheochromocytoma and paraganglioma (PPGLs) are neuroendocrine tumors with diverse clinical presentations. PPGLs can be sporadic but often are associated with various syndromes, which can have variable clinical presentations. A thorough workup is therefore critical for staging, treatment, and follow-up. Imaging is an essential part of the workup and diagnosis of PPGLs., Recent Findings: Improvements in cross-sectional imaging with radionuclides have increased specificity and sensitivity for identifying and treating PPGLs. Furthermore, a variety of targets on PPGLs has allowed for optimal imaging with radionuclides that can be used for staging and treatment. Currently, radionuclides are being evaluated for staging and treatment of PPGLs. Developing novel radionuclides that can identify disease sites and target them simultaneously provides a potential for improving survival and outcomes in patients with PPGLs. Given the clinical diversity among PPGLs, expanding the therapeutic arsenal against locally advanced or metastatic PPGLs can allow clinicians to evaluate and treat PPGLs thoroughly.

Herein, we report the development of an 18 F-labeled, activity-based small-molecule probe targeting the cancer-associated serine hydrolase NCEH1. We undertook a focused medicinal chemistry campaign to simultaneously preserve potent and specific NCEH1 labeling in live cells and animals, while permitting facile 18 F radionuclide incorporation required for PET imaging. The resulting molecule, [ 18 F]JW199, labels active NCEH1 in live cells at nanomolar concentrations and greater than 1000-fold selectivity relative to other serine hydrolases. [ 18 F]JW199 displays rapid, NCEH1-dependent accumulation in mouse tissues. Finally, we demonstrate that [ 18 F]JW199 labels aggressive cancer tumor cells in vivo, which uncovered localized NCEH1 activity at the leading edge of triple-negative breast cancer tumors, suggesting roles for NCEH1 in tumor aggressiveness and metastasis., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The gold standard for diagnosis of cardiac amyloidosis (CA) is endomyocardial biopsy showing Congo red staining followed by mass spectroscopy, but the diagnosis can also be made with high certainty by demonstration of typical cardiac imaging features along with amyloid on biopsy of another involved organ. The use of cardiac imaging techniques to detect amyloid deposits may frequently obviate the need for invasive methods in order to ascertain the presence, and potentially the type, of amyloid deposition. PURPOSE OF REVIEW: We aim to review the evidence behind the development of novel positron emission tomography (PET) radiotracers for demonstrating cardiac amyloid deposition and potentially distinguishing between light-chain (AL) or transthyretin (ATTR) cardiac amyloidosis. RECENT FINDINGS: Multiple recent studies have shown that thioflavin-analogue tracers such as 18 F-florbetapir, 18 F-florbetaben, 18 F-flutemetamol, and 11 C-labeled Pittsburg Compound-B (PiB) may be able to fulfill the unmet need of elucidating the presence of amyloid deposition in the heart. Because they bind to the beta-pleated motif of the amyloid fibril due to their similarity to the thioflavin structure, they could potentially be used to image CA (Table 1). The use of PET amyloid radiotracers shows promise; however, further data is needed to define their overall accuracy and additive value to the care of patients with suspected systemic and/or cardiac amyloidosis.

There is an urgent clinical need for imaging of α-synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bear potential for non-invasive detection of this biomarker in vivo. Here we demonstrate high-affinity binding of the family member anle253b to fibrillar αSyn and present a high-yielding site-selective radiosynthesis route for 11 C radiolabeling using in-situ generated [ 11 C]formaldehyde and reductive methylation. Radio-HPLC of the tracer after incubation with rat serum in vitro shows excellent stability of the molecule. Positron emission tomography in healthy animals is used to assess the pharmacokinetics and biodistribution of the tracer, showing good penetration of the blood-brain barrier and low background binding to the non-pathological brain., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative proteinopathies. These conditions share brain deposition of abnormal protein aggregates, leading to aberrant biochemical, metabolic, functional, and structural changes. Positron emission tomography (PET) is a well-recognized and unique tool for the in vivo assessment of brain neuropathology, and novel PET techniques are emerging for the study of specific protein species. Today, key applications of PET range from early research and clinical diagnostic tools to their use in clinical trials for both participants screening and outcome evaluation. This position article critically reviews the role of distinct PET molecular tracers for different neurodegenerative proteinopathies, highlighting their strengths, weaknesses, and opportunities, with special emphasis on methodological challenges and future applications., (Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

68 Ga-labeled cyclic RGD dimers and trimer were evaluated as PET radiotracers. It was found that the linker group had little impact on α v β 3 binding affinity of RGD dimers, which share similar α v β 3 binding affinity with the RGD trimer despite of their different multiplicity. Biodistribution properties of 68 Ga radiotracers depend on RGD peptides and radiometal chelates. Among the 68 Ga radiotracers evaluated, 68 Ga-I2P-RGD 2 has the best tumor uptake with good tumor-to-background ratios, and is a good PET radiotracer for imaging gliomas., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

PET imaging is a continuously developing clinical tool for the imaging of different markers of cardiovascular diseases. In this article, some important PET tracers for several diseases affecting the heart and the vessels are highlighted; these include myocardial blood flow, atherosclerosis, fatty acid metabolism, and pathologies in the cardiac autonomic nervous system., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The two neuropathological hallmarks of Alzheimer's disease (AD) are amyloid-[Formula: see text] plaques and neurofibrillary tangles of tau protein. Fifteen years ago, Positron Emission Tomography (PET) with Pittsburgh Compound B ( 11 C-PiB) enabled selective in-vivo visualization of amyloid-[Formula: see text] plaque deposits and has since provided valuable information about the role of amyloid-[Formula: see text] deposition in AD. The progression of tau deposition has been shown to be highly associated with neuronal loss, neurodegeneration, and cognitive decline. Until recently it was not possible to visualize tau deposition in-vivo, but several tau PET tracers are now available in different stages of clinical development. To date, no tau tracer has been approved by the Food and Drug Administration for use in the evaluation of AD or other tauopathies, despite very active research efforts. In this paper we review the recent developments in tau PET imaging with a focus on in-vivo findings in AD and discuss the challenges associated with tau tracer development, the status of development and validation of different tau tracers, and the clinical information these provide.

Increased expression of the human epidermal growth factor receptor (HER) protein family are targets in breast cancer for imaging and therapy. Imaging modalities targeting HER2 and HER3 can diagnose breast cancer with a specific, biologically relevant target. Repeat biopsies do not address heterogeneity intratumorally or between primary disease and metastasis. HER2- and HER3-targeted PET is an important tool to diagnose disease in breast cancer and evaluate response to targeted therapies. PET and single photon emission computed tomography with radiolabeled biomolecules can be used to detect and quantify specific targets, conferring a better understanding of the behavior and effectiveness of treatments., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the main instruments for neuroimaging investigation of patients with chronic ataxia. MRI has a predominant diagnostic role in the single patient, based on the visual detection of three patterns of atrophy, namely, spinal atrophy, cortical cerebellar atrophy and olivopontocerebellar atrophy, which correlate with the aetiologies of inherited or sporadic ataxia. In fact spinal atrophy is observed in Friedreich ataxia, cortical cerebellar atrophy in Ataxia Telangectasia, gluten ataxia and Sporadic Adult Onset Ataxia and olivopontocerebellar atrophy in Multiple System Atrophy cerebellar type. The 39 types of dominantly inherited spinocerebellar ataxias show either cortical cerebellar atrophy or olivopontocerebellar atrophy. T2 or T2* weighted MR images can contribute to the diagnosis by revealing abnormally increased or decreased signal with a characteristic distribution. These include symmetric T2 hyperintensity of the posterior and lateral columns of the cervical spinal cord in Friedreich ataxia, diffuse and symmetric hyperintensity of the cerebellar cortex in Infantile Neuro-Axonal Dystrophy, symmetric hyperintensity of the peridentate white matter in Cerebrotendineous Xanthomatosis, and symmetric hyperintensity of the middle cerebellar peduncles and peridentate white matter, cerebral white matter and corpus callosum in Fragile X Tremor Ataxia Syndrome. Abnormally decreased T2 or T2* signal can be observed with a multifocal distribution in Ataxia Telangectasia and with a symmetric distribution in the basal ganglia in Multiple System Atrophy. T2 signal hypointensity lining diffusely the outer surfaces of the brainstem, cerebellum and cerebrum enables diagnosis of superficial siderosis of the central nervous system. The diagnostic role of nuclear medicine techniques is smaller. SPECT and PET show decreased uptake of radiotracers investigating the nigrostriatal system in Multiple System Atrophy and in patients with Fragile X Tremor Ataxia Syndrome. Semiquantitative or quantitative MRI, SPECT and PET data describing structural, microstructural and functional changes of the cerebellum, brainstem, and spinal cord have been widely applied to investigate physiopathological changes in patients with chronic ataxias. Moreover they can track diseases progression with a greater sensitivity than clinical scales. So far, a few small-size and single center studies employed neuroimaging techniques as surrogate markers of treatment effects in chronic ataxias., (© 2018 Elsevier Inc. All rights reserved.)

A series of vasopressin receptor V 1a ligands have been synthesized for positron emission tomography (PET) imaging. The lead compound (1S,5R)-1 ((4-(1H-indol-3-yl)-3-methoxyphenyl) ((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone) and its F-ethyl analog 6c exhibited the best combination of high binding affinity and optimal lipophilicity within the series. (1S,5R)-1 was radiolabeled with 11 C for PET studies. [ 11 CH 3 ](1S,5R)-1 readily entered the mouse (4.7% ID/g tissue) and prairie vole brains (∼2% ID/g tissue) and specifically (30-34%) labeled V 1a receptor. The common animal anesthetic Propofol significantly blocked the brain uptake of [ 11 CH 3 ](1S,5R)-1 in the mouse brain, whereas anesthetics Ketamine and Saffan increased the uptake variability. Future PET imaging studies with V 1a radiotracers in non-human primates should be performed in awake animals or using anesthetics that do not affect the V 1a receptor., (Copyright © 2017. Published by Elsevier Masson SAS.)

Prostate-specific membrane antigen positron emission tomography (PSMA PET) is a relatively new method of imaging prostate cancer that increases diagnostic accuracy in detecting and guiding management in various stages of the disease pathway. Gallium-68-labelled PSMA PET has increased the sensitivity of detection of disease recurrence at low PSA levels, thus allowing an optimal window for salvage treatment. Apart from its use in disease recurrence, PSMA PET has the potential for increasing sensitivity and specificity for primary tumour localisation and in detecting lymph node disease, leading to a more accurate initial staging of the condition. In advanced disease, the use of PSMA PET may be able to assess response to treatment and also guide treatment with radionuclide therapy. Newer ligands under development might provide avenues for theranostic or personalised therapy applications with early data showing high PSA response rates. The rate of translation of PSMA PET into clinical practice has been remarkable. The use of this modality is likely to increase with future efforts to modify the radiotracer including 18 F labelling to improve availability.

During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD). Radionuclide imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), form an attractive approach to quantitatively monitor the ongoing neurodegenerative processes. Although [ 18 F]-FDG has been recently proposed as a potential biomarker for ALS, active targeting of the underlying pathologic molecular processes is likely to unravel further valuable disease information and may help to decipher the pathogenesis of ALS. In this review, we provide an overview of radiotracers that have already been applied in ALS and discuss possible novel targets for in vivo imaging of various pathogenic processes underlying ALS onset and progression.

Clinical/methodical Issue: Magnetic resonance imaging (MRI) of the breast is an indispensable tool in breast imaging for many indications. Several functional parameters with MRI and positron emission tomography (PET) have been assessed for imaging of breast tumors and their combined application is defined as multiparametric imaging. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the hallmarks of cancer and may provide additional specificity., Standard Radiological Methods: Multiparametric and molecular imaging of the breast comprises established MRI parameters, such as dynamic contrast-enhanced MRI, diffusion-weighted imaging (DWI), MR proton spectroscopy ((1)H-MRSI) as well as combinations of radiological and MRI techniques (e. g. PET/CT and PET/MRI) using radiotracers, such as fluorodeoxyglucose (FDG)., Methodical Innovations: Multiparametric and molecular imaging of the breast can be performed at different field-strengths (range 1.5-7 T). Emerging parameters comprise novel promising techniques, such as sodium imaging ((23)Na MRI), phosphorus spectroscopy ((31)P-MRSI), chemical exchange saturation transfer (CEST) imaging, blood oxygen level-dependent (BOLD) and hyperpolarized MRI as well as various specific radiotracers., Achievements: Multiparametric and molecular imaging has multiple applications in breast imaging. Multiparametric and molecular imaging of the breast is an evolving field that will enable improved detection, characterization, staging and monitoring for personalized medicine in breast cancer.

The recent development and introduction of new hybrid imaging devices combining positron emission tomography (PET) technology with magnetic resonance imaging (MRI) opens up new perspectives in clinical molecular imaging. Combining MRI and fluorine-18 choline PET would theoretically produce valuable clinical data in a single imaging session, which can be used for staging, prognosis, and assessment of treatment response. Fluorine-18-sodium fluoride (18F-NaF) is a highly sensitive PET tracer used as a marker of osteoblastic abnormalities. PET imaging with (68)Ga-DOTATATE or DOTATOC has demonstrated promising results for locating metastatic lesions, occasionally with superior sensitivity than whole-body MRI. l-DOPA PET adds data regarding l-DOPA metabolism, which may increase the specificity and sensibility of the study itself. Fluoromisonidazole is known to be not only a useful tracer for determining hypoxic cells but also an efficient hypoxic radiosensitizer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A series of vasopressin receptor V1a ligands have been synthesized for positron emission tomography (PET) imaging. The lead compound (1S,5R)-1 ((4-(1H-indol-3-yl)-3-methoxyphenyl) ((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone) and its F-ethyl analog 6c exhibited the best combination of high binding affinity and optimal lipophilicity within the series. (1S,5R)-1 was radiolabeled with 11C for PET studies. [11CH3](1S,5R)-1 readily entered the mouse (4.7% ID/g tissue) and prairie vole brains (∼2% ID/g tissue) and specifically (30-34%) labeled V1a receptor. The common animal anesthetic Propofol significantly blocked the brain uptake of [11CH3](1S,5R)-1 in the mouse brain, whereas anesthetics Ketamine and Saffan increased the uptake variability. Future PET imaging studies with V1a radiotracers in non-human primates should be performed in awake animals or using anesthetics that do not affect the V1a receptor.