EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy.

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282). RESULTS: The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7-not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8-28.1) in pancreatic, and 17.6 months (14.4-33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity. CONCLUSION: This study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.

Sporadic Creutzfeldt-Jakob disease is associated with reorganization of metabolic connectivity in a pathological brain network.

BACKGROUND AND PURPOSE: Although sporadic Creutzfeldt-Jakob disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, the metabolic brain network associated with sCJD was investigated and its internal network organization was explored. METHODS: We explored 2-[18 F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) brain scans of 29 sCJD patients, 56 normal controls (NCs) and 46 other dementia patients from two independent centers. sCJD-related pattern (CJDRP) was identified in a cohort of 16 pathologically proven sCJD patients and 16 age-matched NCs using scaled subprofile modeling/principal component analysis and was prospectively validated in an independent cohort of 13 sCJD patients and 20 NCs. The pattern's specificity was tested on other dementia patients and its clinical relevance by clinical correlations. The pattern's internal organization was further studied using graph theory methods. RESULTS: The CJDRP was characterized by relative hypometabolism in the bilateral caudate, thalami, middle and superior frontal gyri, parietal lobe and posterior cingulum in association with relative hypermetabolism in the hippocampi, parahippocampal gyri and cerebellum. The pattern's expression significantly discriminated sCJD from NCs and other dementia patients (p < 0.005; receiver operating characteristic analysis CJD vs. NCs area under the curve [AUC] 0.90-0.96, sCJD vs. Alzheimer's disease AUC 0.78, sCJD vs. behavioral variant of frontotemporal dementia AUC 0.84). The pattern's expression significantly correlated with cognitive, functional decline and disease duration. The metabolic connectivity analysis revealed inefficient information transfer with specific network reorganization. CONCLUSIONS: The CJDRP is a robust metabolic biomarker of sCJD. Due to its excellent clinical correlations it has the potential to monitor disease in emerging disease-modifying trials.

Evaluation of the role of thyroid scintigraphy in the differential diagnosis of thyrotoxicosis.

OBJECTIVE: A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH-R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third-generation TRAb are not available. First-generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first-generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first-generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism. METHODS: We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first-generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis. RESULTS: Seventy-three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves' disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%). CONCLUSIONS: Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first-generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first-generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.

EANM practice guideline/SNMMI procedure standard for dopaminergic imaging in Parkinsonian syndromes 1.0.

PURPOSE: This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes. METHODS: Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally, [18F]fluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for [18F]fluorodopa imaging in this setting are still lacking. CONCLUSION: All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.

Multicenter Validation of Metabolic Abnormalities Related to PSP According to the MDS-PSP Criteria.

It remains unclear whether the supportive imaging features described in the diagnostic criteria for progressive supranuclear palsy (PSP) are suitable for the full clinical spectrum. The aim of the current study was to define and cross-validate the pattern of glucose metabolism in the brain associated with a diagnosis of different PSP variants. A retrospective multicenter cohort study performed on 73 PSP patients who were referred for a fluorodeoxyglucose positron emission tomography PET scan: PSP-Richardson's syndrome, n = 47; PSP-parkinsonian variant, n = 18; and progressive gait freezing, n = 8. In addition, we included 55 healthy controls and 58 Parkinson's disease (PD) patients. Scans were normalized by global mean activity. We analyzed the regional differences in metabolism between the groups. Moreover, we applied a multivariate analysis to obtain a PSP-related pattern that was cross-validated in independent populations at the individual level. Group analysis showed relative hypometabolism in the midbrain, basal ganglia, thalamus, and frontoinsular cortices and hypermetabolism in the cerebellum and sensorimotor cortices in PSP patients compared with healthy controls and PD patients, the latter with more severe involvement in the basal ganglia and occipital cortices. The PSP-related pattern obtained confirmed the regions described above. At the individual level, the PSP-related pattern showed optimal diagnostic accuracy to distinguish between PSP and healthy controls (sensitivity, 80.4%; specificity, 96.9%) and between PSP and PD (sensitivity, 80.4%; specificity, 90.7%). Moreover, PSP-Richardson's syndrome and PSP-parkinsonian variant patients showed significantly more PSP-related pattern expression than PD patients and healthy controls. The glucose metabolism assessed by fluorodeoxyglucose PET is a useful and reproducible supportive diagnostic tool for PSP-Richardson's syndrome and PSP-parkinsonian variant. © 2020 International Parkinson and Movement Disorder Society.

Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0.

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.

Automated assessment of FDG-PET for differential diagnosis in patients with neurodegenerative disorders.

PURPOSE: To review literature until November 2015 and reach a consensus on whether automatic semi-quantification of brain FDG-PET is useful in the clinical setting for neurodegenerative disorders. METHODS: A literature search was conducted in Medline, Embase, and Google Scholar. Papers were selected with a lower limit of 30 patients (no limits with autopsy confirmation). Consensus recommendations were developed through a Delphi procedure, based on the expertise of panelists, who were also informed about the availability and quality of evidence, assessed by an independent methodology team. RESULTS: Critical outcomes were available in nine among the 17 papers initially selected. Only three papers performed a direct comparison between visual and automated assessment and quantified the incremental value provided by the latter. Sensitivity between visual and automatic analysis is similar but automatic assessment generally improves specificity and marginally accuracy. Also, automated assessment increases diagnostic confidence. As expected, performance of visual analysis is reported to depend on the expertise of readers. CONCLUSIONS: Tools for semi-quantitative evaluation are recommended to assist the nuclear medicine physician in reporting brain FDG-PET pattern in neurodegenerative conditions. However, heterogeneity, complexity, and drawbacks of these tools should be known by users to avoid misinterpretation. Head-to-head comparisons and an effort to harmonize procedures are encouraged.

Clinical utility of FDG-PET in amyotrophic lateral sclerosis and Huntington's disease.

AIM: To evaluate the incremental value of FDG-PET over clinical tests in: (i) diagnosis of amyotrophic lateral sclerosis (ALS); (ii) picking early signs of neurodegeneration in patients with a genetic risk of Huntington's disease (HD); and detecting metabolic changes related to cognitive impairment in (iii) ALS and (iv) HD patients. METHODS: Four comprehensive literature searches were conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on these four diagnostic scenarios. RESULTS: The availability of evidence was good for FDG-PET utility to support the diagnosis of ALS, poor for identifying presymptomatic subjects carrying HD mutation who will convert to HD, and lacking for identifying cognitive-related metabolic changes in both ALS and HD. After the Delphi consensual procedure, the panel did not support the clinical use of FDG-PET for any of the four scenarios. CONCLUSION: Relative to other neurodegenerative diseases, the clinical use of FDG-PET in ALS and HD is still in its infancy. Once validated by disease-control studies, FDG-PET might represent a potentially useful biomarker for ALS diagnosis. FDG-PET is presently not justified as a routine investigation to predict conversion to HD, nor to detect evidence of brain dysfunction justifying cognitive decline in ALS and HD.

Clinical utility of FDG-PET for the clinical diagnosis in MCI.

PURPOSE: We aim to report the quality of accuracy studies investigating the utility of [18F]fluorodeoxyglucose (FDG)-PET in supporting the diagnosis of prodromal Alzheimer's Disease (AD), frontotemporal lobar degeneration (FTLD) and prodromal dementia with Lewy bodies (DLB) in mild cognitive impairment (MCI) subjects, and the corresponding recommendations made by a panel of experts. METHODS: Seven panellist, four from the European Association of Nuclear Medicine, and three from the European Academy of Neurology, produced recommendations taking into consideration the incremental value of FDG-PET, as added on clinical-neuropsychological examination, to ascertain the aetiology of MCI (AD, FTLD or DLB). A literature search using harmonized population, intervention, comparison, and outcome (PICO) strings was performed, and an evidence assessment consistent with the European Federation of Neurological Societies guidance was provided. The consensual recommendation was achieved based on Delphi rounds. RESULTS: Fifty-four papers reported the comparison of interest. The selected papers allowed the identification of FDG patterns that characterized MCI due to AD, FTLD and DLB. While clinical outcome studies supporting the diagnosis of MCI due to AD showed varying accuracies (ranging from 58 to 100%) and varying areas under the receiver-operator characteristic curves (0.66 to 0.97), no respective data were identified for MCI due to FTLD or for MCI due to DLB. However, the high negative predictive value of FDG-PET and the existence of different disease-specific patterns of hypometabolism support the consensus recommendations for the clinical use of this imaging technique in MCI subjects. CONCLUSIONS: FDG-PET has clinical utility on a fair level of evidence in detecting MCI due to AD. Although promising also in detecting MCI due to FTLD and MCI due to DLB, more research is needed to ultimately judge the clinical utility of FDG-PET in these entities.

Diagnostic utility of FDG-PET in the differential diagnosis between different forms of primary progressive aphasia.

PURPOSE: A joint effort of the European Association of Nuclear Medicine (EANM) and the European Academy of Neurology (EAN) aims at clinical guidance for the use of FDG-PET in neurodegenerative diseases. This paper addresses the diagnostic utility of FDG-PET over clinical/neuropsychological assessment in the differentiation of the three forms of primary progressive aphasia (PPA). METHODS: Seven panelists were appointed by the EANM and EAN and a literature search was performed by using harmonized PICO (Population, Intervention, Comparison, Outcome) question keywords. The studies were screened for eligibility, and data extracted to assess their methodological quality. Critical outcomes were accuracy indices in differentiating different PPA clinical forms. Subsequently Delphi rounds were held with the extracted data and quality assessment to reach a consensus based on both literature and expert opinion. RESULTS: Critical outcomes for this PICO were available in four of the examined papers. The level of formal evidence supporting clinical utility of FDG-PET in differentiating among PPA variants was considered as poor. However, the consensual recommendation was defined on Delphi round I, with six out of seven panelists supporting clinical use. CONCLUSIONS: Quantitative evidence demonstrating utility or lack thereof is still missing. Panelists decided consistently to provide interim support for clinical use based on the fact that a typical atrophy or metabolic pattern is needed for PPA according to the diagnostic criteria, and the synaptic failure detected by FDG-PET is an earlier phenomenon than atrophy. Also, a normal FDG-PET points to a non-neurodegenerative cause.

Diagnostic utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in asymptomatic subjects at increased risk for Alzheimer's disease.

PURPOSE: To assess the clinical utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of early signs of neurodegeneration in conditions of increased risk for Alzheimer's disease (AD) as defined by: subjective cognitive decline (SCD), evidence of cerebral amyloid-pathology, apolipoprotein E (APOE) ε4-positive genotype, or autosomal dominant forms of AD (ADAD) in asymptomatic stages. METHODS: A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on three different diagnostic scenarios. RESULTS: The level of empirical study evidence for the use of FDG-PET to detect meaningful early signs of neurodegeneration was considered to be poor for ADAD and lacking for SCD and asymptomatic persons at risk, based on APOE ε4-positive genotype or cerebral amyloid pathology. Consequently, and consistent with current diagnostic criteria, panelists decided not to recommend routine clinical use of FDG-PET in these situations and to currently mainly reserve it for research purposes. CONCLUSION: Currently, there is limited evidence on which to base recommendations regarding the clinical routine use of FDG-PET to detect diagnostically meaningful early signs of neurodegeneration in asymptomatic subjects with ADAD, with APOE ε4-positive genotype, or with cerebral amyloid pathology, and in subjects with SCD. Future prospective studies are warranted and in part already ongoing, aiming to assess the added value of FDG-PET in this context beyond research applications.

Clinical utility of FDG PET in Parkinson's disease and atypical parkinsonism associated with dementia.

PURPOSE: There are no comprehensive guidelines for the use of FDG PET in the following three clinical scenarios: (1) diagnostic work-up of patients with idiopathic Parkinson's disease (PD) at risk of future cognitive decline, (2) discriminating idiopathic PD from progressive supranuclear palsy, and (3) identifying the underlying neuropathology in corticobasal syndrome. METHODS: We therefore performed three literature searches and evaluated the selected studies for quality of design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were the sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiving operating characteristic curve, and positive/negative likelihood ratio of FDG PET in detecting the target condition. Using the Delphi method, a panel of seven experts voted for or against the use of FDG PET based on published evidence and expert opinion. RESULTS: Of 91 studies selected from the three literature searches, only four included an adequate quantitative assessment of the performance of FDG PET. The majority of studies lacked robust methodology due to lack of critical outcomes, inadequate gold standard and no head-to-head comparison with an appropriate reference standard. The panel recommended the use of FDG PET for all three clinical scenarios based on nonquantitative evidence of clinical utility. CONCLUSION: Despite widespread use of FDG PET in clinical practice and extensive research, there is still very limited good quality evidence for the use of FDG PET. However, in the opinion of the majority of the panellists, FDG PET is a clinically useful imaging biomarker for idiopathic PD and atypical parkinsonism associated with dementia.

Clinical utility of FDG-PET for the differential diagnosis among the main forms of dementia.

AIM: To assess the clinical utility of FDG-PET as a diagnostic aid for differentiating Alzheimer's disease (AD; both typical and atypical forms), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD) and non-degenerative pseudodementia. METHODS: A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted on six different diagnostic scenarios using the Delphi method. RESULTS: The level of empirical study evidence for the use of FDG-PET was considered good for the discrimination of DLB and AD; fair for discriminating FTLD from AD; poor for atypical AD; and lacking for discriminating DLB from FTLD, AD from VaD, and for pseudodementia. Delphi voting led to consensus in all scenarios within two iterations. Panellists supported the use of FDG-PET for all PICOs-including those where study evidence was poor or lacking-based on its negative predictive value and on the assistance it provides when typical patterns of hypometabolism for a given diagnosis are observed. CONCLUSION: Although there is an overall lack of evidence on which to base strong recommendations, it was generally concluded that FDG-PET has a diagnostic role in all scenarios. Prospective studies targeting diagnostically uncertain patients for assessing the added value of FDG-PET would be highly desirable.

Role of amino-acid PET in high-grade gliomas: limitations and perspectives.

Positron emission tomography (PET) using radiolabeled amino-acids was recently recommended by the Response Assessment in Neuro-Oncology (RANO) working group as an additional tool in the diagnostic assessment of brain tumors. The aim of this review is to summarize available literature data on the role of amino-acid PET imaging in high-grade gliomas (HGGs), with regard to diagnosis, treatment planning and follow-up of these tumors. Indeed, amino-acid PET applications are multiple throughout the evolution of HGGs. However, certain limitations such as lack of specificity, uncertain value for grading and prognostication or the limited data for treatment monitoring should to be taken into account, the latter of which are further developed in this review. Notwithstanding these limitations, amino-acid PET is becoming increasingly accessible in many nuclear medicine centers. Larger prospective cohort prospective studies are thus needed in order to increase the clinical value of this modality and enable its extended use to the largest number of patients.

Emerging clinical issues and multivariate analyses in PET investigations.

PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET) has been gradually introduced in the diagnostic clinical criteria of the most prevalent neurodegenerative diseases. Moreover, an increasing amount of literature has shown that the information provided by FDG-PET enhances the sensitivity of standard imaging biomarkers in less frequent disorders in which an early differential diagnosis can be of paramount relevance for patient management and outcome. Therefore emerging uses of FDG-PET may be important in prion diseases, autoimmune encephalitis (AE) and amyotrophic lateral sclerosis. Interestingly, FDG-PET findings can also be observed in the early phases of these conditions, even in the presence of normal magnetic resonance imaging scans. Thalamic hypometabolism is a common finding in sporadic Creutzfeldt-Jacob disease and fatal familiar insomnia patients, with further cortical synaptic dysfunction in the former. Limbic and extra-limbic metabolic abnormalities (more often hypermetabolism) can be observed in AE, although specific patterns may be seen within different syndromes associated with antibodies that target neuronal surface or synaptic antigens. FDG-PET shows its usefulness by discriminating patients with amyotrophic lateral sclerosis associated to upper motor neuron onset that evolve to frontotemporal dementia. Besides visual and voxel based image analysis, multivariate analysis as interregional correlation analysis and independent/principal component analysis have been successfully implemented to PET images increasing the accuracy of the discrimination of neurodegenerative diseases. The clinical presentation and current diagnostic criteria of these neurologic disorders as well as the emerging usefulness of FDG-PET in the diagnostic workup are presented and discussed in this review.

Imaging approaches to assess the therapeutic response of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): current perspectives and future trends of an exciting field in development.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a family of neoplasms with a complex spectrum of clinical behavior. Although generally more indolent than carcinomas, once they progress beyond surgical resectability, they are essentially incurable. Systemic treatment options have substantially expanded in recent years for the management of advanced disease. Imaging plays a major role in new drug development, as it is the main tool used to objectively evaluate response to novel agents. However, current standard response criteria have proven suboptimal for the assessment of the antiproliferative effect of many targeted agents, particularly in the context of slow-growing tumors such as well-differentiated NETs. The aims of this article are to discuss the advantages and limitations of conventional radiological techniques and standard response assessment criteria and to review novel imaging modalities in development as well as alternative cancer- and therapy-specific criteria to assess drug efficacy in the field of GEP-NETs.