{"title":"Advances With <sup>225</sup>Ac-DOTATATE Targeted Alpha Therapy in Somatostatin Receptor Positive Neuroendocrine Tumors.","authors":"Kunal Ramesh Chandekar, Chandrasekhar Bal","doi":"10.1053/j.semnuclmed.2025.06.008","DOIUrl":"https://doi.org/10.1053/j.semnuclmed.2025.06.008","url":null,"abstract":"<p><p><sup>225</sup>Ac-DOTATATE-based targeted alpha therapy (TAT) is emerging as a transformative option in the management of advanced, well-differentiated, somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs), particularly in patients refractory to conventional β-emitter peptide receptor radionuclide therapy (PRRT). This review synthesizes current evidence from preclinical models and early-phase clinical studies, highlighting its therapeutic promise in terms of potent antitumor efficacy and favorable toxicity profile. We discuss the radiobiological and mechanistic advantages of α-particle therapy while also addressing key limitations such as radionuclide supply constraints, recoil-induced daughter redistribution, challenges in dosimetry, and regulatory hurdles. Emerging strategies including improved chelators, SSTR antagonists, and tandem or combination therapies are described. Key ongoing trials have also been summarized. As <sup>225</sup>Ac-DOTATATE-based TAT progresses toward mainstream clinical integration, multidisciplinary collaboration across academia, industry, and regulatory bodies will be essential to refine protocols, optimize safety, and expand access.</p>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matilde Nerattini , Elisabetta Maria Abenavoli , Valentina Berti
{"title":"PET/CT in Movement Disorders: Update","authors":"Matilde Nerattini , Elisabetta Maria Abenavoli , Valentina Berti","doi":"10.1053/j.semnuclmed.2025.03.007","DOIUrl":"10.1053/j.semnuclmed.2025.03.007","url":null,"abstract":"<div><div>This review synthesizes recent literature, primarily from the last 5 years, to highlight the impact of innovative technologies and analytical approaches on the application of positron emission tomography (PET) in movement disorders. PET remains a cornerstone for investigating these conditions, with recent advancements enhancing our understanding of disease pathophysiology and progression. Established findings, such as the ability of [<sup>18</sup>F]-fluorodeoxyglucose PET (18F-FDG PET) to differentiate Parkinson's disease (PD) from atypical parkinsonian syndromes based on characteristic metabolic patterns, have been consistently validated. PD typically presents with relative hypermetabolism in the basal ganglia, thalamus and cerebellum, while atypical parkinsonisms exhibit more widespread subcortical hypometabolism. Technological innovations, particularly in quantification methods and metabolic connectivity analysis, have improved diagnostic precision and provided deeper insights into disease mechanisms. Dopaminergic PET imaging, crucial for assessing presynaptic and postsynaptic dysfunction, has also benefited from these advances. The field is further evolving with the development of novel tracers targeting pathological hallmarks, such as alpha-synuclein in PD and multiple system atrophy (MSA), tau in progressive supranuclear palsy (PSP) and cortico-basal degeneration (CBD), and tracers for neuroinflammation, microglial activation, and neurotransmitter systems like serotonin and acetylcholine. While PET is not yet routinely used for the clinical assessment of Huntington's disease or ataxia, research applications are expanding, driven by the potential of these new tracers and analytical techniques. These advancements not only reinforce existing knowledge but also open new avenues for enhancing the understanding and management of movement disorders.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 565-576"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Positron Emission Tomography in Autism Spectrum Disorder: Current Status and Future Perspectives","authors":"Jeongryul Ryu, Minyoung Oh","doi":"10.1053/j.semnuclmed.2025.06.003","DOIUrl":"10.1053/j.semnuclmed.2025.06.003","url":null,"abstract":"<div><div>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social communication and the presence of repetitive behaviors. While both genetic and environmental factors are known to contribute to ASD, its precise causes remain unclear. Advances in molecular imaging, particularly positron emission tomography (PET), have enhanced our ability to investigate the neurobiological mechanisms underlying ASD. PET offers valuable insights into brain metabolism, neurotransmitter systems, neuroinflammation, and synaptic density. This review highlights the contributions of PET imaging to understanding the pathophysiology of ASD, focusing on recent advancements in technology and novel radiotracers. These innovations may lead to more accurate biomarkers for diagnosis and targeted therapeutic strategies. As PET technology continues to improve, it holds significant potential for advancing ASD research and clinical applications.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 605-615"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weiyuan Lin , Chongyi Huang , Zhiqiang Tan , Hao Xu , Weijun Wei , Lu Wang
{"title":"CuII-bis(thioureido) Complex: A Potential Radiotracer for Detecting Oxidative Stress and Neuroinflammation in Neurodegenerative Diseases","authors":"Weiyuan Lin , Chongyi Huang , Zhiqiang Tan , Hao Xu , Weijun Wei , Lu Wang","doi":"10.1053/j.semnuclmed.2025.03.008","DOIUrl":"10.1053/j.semnuclmed.2025.03.008","url":null,"abstract":"<div><div>Neurodegenerative diseases, characterized by progressive neuronal degeneration and associated with neuroinflammation and oxidative stress, present significant challenges in diagnosis and treatment. This review explores the potential of copper(II)-bis(thiosemicarbazone) complexes, particularly Cu-ATSM, as a dual-purpose radiopharmaceutical for imaging and therapeutic interventions. Cu-ATSM exhibits unique redox-dependent retention in pathological microenvironments, driven by mitochondrial dysfunction and hyper-reductive states, which enables the noninvasive detection of oxidative stress via positron emission tomography (PET). Preclinical studies demonstrate its efficacy in mitigating neuroinflammation by suppressing glial activation, reducing the secretion of pro-inflammatory cytokines (e.g., TNF-α, MCP-1), and increasing the expression of neuroprotective metallothionein-1 (MT1). Some Clinical research reveals elevated ⁶⁴Cu-ATSM uptake in Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS) patients, correlating with disease severity and regional oxidative stress markers. Furthermore, Cu-ATSM derivatives show promise in modulating blood-brain barrier (BBB) permeability, enhancing amyloid-β clearance, and restoring copper homeostasis in ALS models. Despite these advances, limitations such as small cohort sizes and heterogeneity in clinical studies underscore the need for larger-scale validation. Multimodal imaging integrating PET and MRI, alongside novel structural analogs targeting Aβ plaques and redox imbalances, emerges as a strategic direction for future research. Collectively, Cu-ATSM represents a transformative tool for elucidating neuropathological mechanisms and advancing therapeutic strategies in neurodegenerative disorders.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 577-586"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rodolfo Ferrando , Daniel Hernandes , Bruno Galafassi Ghini , Artur Martins Coutinho
{"title":"PET Imaging in Psychiatric Disorders","authors":"Rodolfo Ferrando , Daniel Hernandes , Bruno Galafassi Ghini , Artur Martins Coutinho","doi":"10.1053/j.semnuclmed.2025.06.004","DOIUrl":"10.1053/j.semnuclmed.2025.06.004","url":null,"abstract":"<div><div>Positron emission tomography (PET) has emerged as a pivotal imaging modality in the investigation of psychiatric disorders, enabling in vivo assessment of regional cerebral metabolism, neurotransmitter dynamics, receptor binding, synaptic density, and neuroinflammation. This comprehensive review synthesizes current evidence on the utility of PET imaging in elucidating the pathophysiology of major psychiatric conditions—including schizophrenia, mood disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, and addiction and its potential in clinical decision-making. <sup>18</sup>F-FDG-PET has consistently demonstrated regional metabolic abnormalities, most notably prefrontal hypometabolism in schizophrenia and major depressive disorder, with implications for negative symptomatology, cognitive dysfunction, and treatment resistance. Functional FDG-PET (fPET) has recently enabled dynamic metabolic mapping with high temporal resolution, allowing the evaluation of stimulus-induced changes in neuronal activity. Receptor-specific PET tracers have provided further insights into dopaminergic, serotonergic, glutamatergic, and GABAergic dysregulation across psychiatric spectra. Notably, schizophrenia is associated with a increased striatal dopamine (DA) synthesis capacity and DA release, and disrupted frontolimbic connectivity, while depression shows reduced serotonergic transporter binding and lower mGluR5 availability, supporting neurotransmitter system-based subtyping. PET imaging has also revealed neuroinflammatory signatures, such as altered TSPO binding, as well as synaptic density reductions via SV2A tracers in early psychosis, emphasizing shared neurobiological underpinnings and disease progression markers. In pediatric and neurodevelopmental disorders, including ASD, PET and multimodal approaches have contributed to identifying heterogeneous neurochemical phenotypes, linking abnormal glucose metabolism and receptor availability to specific behavioral domains. Clinically, PET imaging aids in the differential diagnosis of primary psychiatric disorders from neurodegenerative conditions, including behavioral variant frontotemporal dementia (bvFTD), by detecting disease-specific metabolic patterns and supporting biomarker-informed diagnostics. Furthermore, PET has been employed to predict and monitor treatment response across pharmacological and neuromodulatory interventions, including antidepressants, electroconvulsive therapy (ECT), and cognitive behavioral therapy (CBT), enabling strides toward personalized psychiatric care. Despite its promise, widespread clinical integration of PET in psychiatry remains limited by high cost, accessibility barriers, and the need for standardized acquisition and interpretation protocols. Ongoing advancements in radiopharmaceutical development, artificial intelligence, and normative imaging databases are expected to facilitate the incorporation of PET into routine psychiatric assessment a","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 587-604"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katarzyna Barańska , Katarzyna Niemas , Kacper Pełka , Jolanta Kunikowska
{"title":"PET/CT in the Imaging of CNS Tumors","authors":"Katarzyna Barańska , Katarzyna Niemas , Kacper Pełka , Jolanta Kunikowska","doi":"10.1053/j.semnuclmed.2025.04.002","DOIUrl":"10.1053/j.semnuclmed.2025.04.002","url":null,"abstract":"<div><div>Central nervous system (CNS) tumors are quite rare but cause significant morbidity and mortality. Positron Emission Tomography (PET) is a widely utilized imaging modality within the field of nuclear medicine. CNS tumor diagnostics are an essential tool in the diagnosis and treatment of patients with glioma, offering valuable insights into tumor characteristics, treatment response and outcomes. A variety of different tracers are used in PET imaging of brain tumors including <sup>18</sup>F-labeled fluorodeoxyglucose ([<sup>18</sup>F]FDG), markers showing amino acid metabolism, angiogenesis or inflammatory processes. In this article we describe possibility of use different tracers in different clinical scenario of CNS tumors.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 475-486"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gilles N. Stormezand , Janine Doorduin , Andor W.J.M. Glaudemans , Anouk van der Hoorn , Bauke M. De Jong
{"title":"Current Developments on [18F]FDG PET/CT in Inflammatory Disorders of the Central Nervous System","authors":"Gilles N. Stormezand , Janine Doorduin , Andor W.J.M. Glaudemans , Anouk van der Hoorn , Bauke M. De Jong","doi":"10.1053/j.semnuclmed.2025.06.001","DOIUrl":"10.1053/j.semnuclmed.2025.06.001","url":null,"abstract":"<div><div>2-Deoxy-2-[<sup>18</sup>F]fluoro-D-glucose positron emission tomography (FDG-PET) is widely used to study cerebral glucose metabolism and may be useful in several inflammatory disorders of the central nervous system. Emerging literature suggests that [<sup>18</sup>F]FDG may be more sensitive to detect abnormalities in auto-immune encephalitis (AIE) in comparison to MRI, especially in NDMA receptor encephalitis. Distinct patterns of regional abnormalities in AIE have been reported, depending on the auto-antibody involved. Predominant findings are hypermetabolism of the mediotemporal lobe and hypometabolism in parietal and occipital lobes. The possibility for whole body imaging in the setting of malignancy screening further strengthens the importance of [<sup>18</sup>F]FDG PET in AIE when associated with paraneoplastic syndromes. Other inflammatory conditions of the central nervous system where [<sup>18</sup>]FDG PET may facilitate diagnosis include neurosarcoidosis and potential neuropsychiatric manifestations of systemic lupus erythematodes. More recently, [<sup>18</sup>F]FDG PET has been used in patients to evaluate postacute sequelae of COVID-19, allowing assessment of specific neuronal impairments at the individual level and determination of time-dependent metabolic alterations.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 503-511"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artificial Intelligence Augmented Cerebral Nuclear Imaging","authors":"Geoffrey M. Currie , K. Elizabeth Hawk","doi":"10.1053/j.semnuclmed.2025.05.005","DOIUrl":"10.1053/j.semnuclmed.2025.05.005","url":null,"abstract":"<div><div>Artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has significant potential to advance the capabilities of nuclear neuroimaging. The current and emerging applications of ML and DL in the processing, analysis, enhancement and interpretation of SPECT and PET imaging are explored for brain imaging. Key developments include automated image segmentation, disease classification, and radiomic feature extraction, including lower dimensionality first and second order radiomics, higher dimensionality third order radiomics and more abstract fourth order deep radiomics. DL-based reconstruction, attenuation correction using pseudo-CT generation, and denoising of low-count studies have a role in enhancing image quality. AI has a role in sustainability through applications in radioligand design and preclinical imaging while federated learning addresses data security challenges to improve research and development in nuclear cerebral imaging. There is also potential for generative AI to transform the nuclear cerebral imaging space through solutions to data limitations, image enhancement, patient-centered care, workflow efficiencies and trainee education. Innovations in ML and DL are re-engineering the nuclear neuroimaging ecosystem and reimagining tomorrow’s precision medicine landscape.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 616-628"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Update on Molecular Imaging in Epilepsy","authors":"Kowshik Vengadesan , Ankita Phulia , Rakesh Kumar","doi":"10.1053/j.semnuclmed.2025.05.007","DOIUrl":"10.1053/j.semnuclmed.2025.05.007","url":null,"abstract":"<div><div>Epilepsy is one of the commonest neurological disorders worldwide. It is characterized by recurrent unprovoked seizures and has significant effects on one’s daily life. Though almost two thirds of patients with epilepsy respond well with one or more antiepileptic drugs, about 30% patients suffer with drug resistant epilepsy (DRE). Patients with focal variant of DRE, often have a focal pathology in brain and benefit vastly by removing or disconnecting the foci of origin of epileptiform waves from other parts of the cerebral cortex. While clinical examination, MRI and EEG are the first line investigations done in such patients before surgery, many a times they yield normal or discordant or multiple lesions of which only 1 or 2 are epileptogenic. It is in such cases; molecular imaging such as SPECT and PET helps in accurately demarcating the EZ for planning epilepsy surgery. The functional integrity of the rest of the brain can also be assessed by PET and SPECT, which may also offer valuable insights into the potential pathophysiology of the neurocognitive and behavioral impairments commonly seen in these patients. Epilepsy continues to be a common indication for perfusion SPECT as it is the only imaging method that can visualize the ictal onset zone in vivo. Interictal FDG PET/CT is a single investigation that can provide most information about EZ whereas SPECT has to be done twice—ictal and interictal. The evolution of advanced image analysis techniques like SISCOM, SISCOS, PISCOM and newer receptor-based PET tracers has further refined the localization of the seizure onset zone.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 487-502"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"18F-FDG PET for Dementia Evaluation: Co-pathologies, New Diseases, and Its Roles in the Era of Antiamyloid Treatment","authors":"Tanyaluck Thientunyakit , Weerasak Muangpaisan , Satoshi Minoshima","doi":"10.1053/j.semnuclmed.2025.04.007","DOIUrl":"10.1053/j.semnuclmed.2025.04.007","url":null,"abstract":"<div><div>Dementia, which impairs a person's cognition and ability in daily tasks and is often caused by neurodegenerative disorders, remains one of the most challenging neuropsychiatric conditions. The prevalence of dementia has been steadily increasing in aging societies. Recently, antiamyloid treatment has been developed and approved for the treatment of Alzheimer’s disease (AD), which is known as the major cause of dementia. Such therapeutic developments have accelerated the use of in vivo biomarkers in research, clinical trials, and clinical practice. Past and recent developments of several biomarkers, including <sup>18</sup>F-fluorodeoxyglucose (FDG) positron emission tomography (PET), have played a pivotal role in understanding the underlying mechanisms of dementing disorders and accelerating progress in both research and clinical practice, leading to more accurate clinical diagnosis, recognition of co-pathologies, better understanding of new diseases, treatment planning, and response evaluation. This article reviews the roles of brain FDG PET, one of the well-established imaging biomarkers, as a valuable tool for studying brain metabolism and its applications in clinical and research settings, particularly for the treatment of dementia.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 4","pages":"Pages 526-537"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}