Pub Date : 2025-09-01Epub Date: 2025-05-26DOI: 10.1053/j.semnuclmed.2025.05.002
Dirk Bender
The strength of Nuclear Medicine imaging are the compounds to be used as radioactive probes. Unfortunately there are many constraints both in relation to physiological parameters such as metabolism as well to compound related properties like lipophilicity or chemical stability. Due these constraints, many, otherwise promising, compounds could not be used in Nuclear Medicine imaging. Within this review a brief summary is given regarding possible limitations for imaging probes and approaches or techniques to overcome the constraints. Even so the review focuses on imaging with central active compounds, many of these problems appear likewise when targeting peripheral organs. Besides the established approaches to overcome limitations some new, so far not explored, directions are discussed. Finally, a potential new tool in imaging will be presented, a trojan horse approach for transportation of radioligands. Here, like in conventional drug development, lipid nanoparticles may have potential to be used as carrier systems in Nuclear Medicine as well. This, so far not explored, concept is briefly presented.
{"title":"New Radiopharmaceutical Tools in Imaging","authors":"Dirk Bender","doi":"10.1053/j.semnuclmed.2025.05.002","DOIUrl":"10.1053/j.semnuclmed.2025.05.002","url":null,"abstract":"<div><div>The strength of Nuclear Medicine imaging are the compounds to be used as radioactive probes. Unfortunately there are many constraints both in relation to physiological parameters such as metabolism as well to compound related properties like lipophilicity or chemical stability. Due these constraints, many, otherwise promising, compounds could not be used in Nuclear Medicine imaging. Within this review a brief summary is given regarding possible limitations for imaging probes and approaches or techniques to overcome the constraints. Even so the review focuses on imaging with central active compounds, many of these problems appear likewise when targeting peripheral organs. Besides the established approaches to overcome limitations some new, so far not explored, directions are discussed. Finally, a potential new tool in imaging will be presented, a trojan horse approach for transportation of radioligands. Here, like in conventional drug development, lipid nanoparticles may have potential to be used as carrier systems in Nuclear Medicine as well. This, so far not explored, concept is briefly presented.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 789-794"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161566","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}
Pub Date : 2025-09-01Epub Date: 2024-06-21DOI: 10.1053/j.semnuclmed.2024.05.003
Andrew Dullea , Lydia O'Sullivan , Kirsty K. O'Brien , Marie Carrigan , Susan Ahern , Maeve McGarry , Patricia Harrington , Kieran A. Walsh , Susan M. Smith , Máirín Ryan
The aim of this overview was to consolidate existing evidence syntheses and provide a comprehensive overview of the evidence for 18F-prostate specific membrane antigen (PSMA) PET/CT in the staging of high-risk prostate cancer and restaging after biochemical recurrence. An overview of reviews was performed and reported in line with the preferred reporting items for overview of reviews (PRIOR) statement and synthesis without meta-analysis (SWiM) reporting guidelines. A comprehensive database and grey literature search were conducted up to July 18, 2023. Systematic reviews were assessed using the risk of bias in systematic reviews (ROBIS) tool. The certainty of the evidence was assessed using grading of recommendations, assessment, development and evaluations (GRADE). 11 systematic reviews were identified; 10 were at high or unclear risk of bias. Evidence reported on a per-patient, per-lymph node, and per-lesion basis for sensitivity, specificity and overall accuracy was identified. There was a lack of data on dose, adverse events and evidence directly comparing 18F-PSMA PET/CT to other imaging modalities. Evidence with moderate to very low certainty indicated high sensitivity, specificity and accuracy of 18F-PSMA PET/CT in patients with high-risk prostate cancer and biochemical recurrence. There was considerably lower certainty evidence and greater variability in effect estimates for outcomes for the combined intermediate/high-risk cohort. While evidence gaps remain for some outcomes, and most systematic reviews were at high or unclear risk of bias, the current evidence base is broadly supportive of 18F-PSMA PET/CT imaging in the staging and restaging of patients with high-risk prostate cancer and biochemical recurrence.
{"title":"Diagnostic Accuracy of 18F-Prostate Specific Membrane Antigen (PSMA) PET/CT Radiotracers in Staging and Restaging of Patients With High-Risk Prostate Cancer or Biochemical Recurrence: An Overview of Reviews","authors":"Andrew Dullea , Lydia O'Sullivan , Kirsty K. O'Brien , Marie Carrigan , Susan Ahern , Maeve McGarry , Patricia Harrington , Kieran A. Walsh , Susan M. Smith , Máirín Ryan","doi":"10.1053/j.semnuclmed.2024.05.003","DOIUrl":"10.1053/j.semnuclmed.2024.05.003","url":null,"abstract":"<div><div>The aim of this overview was to consolidate existing evidence syntheses and provide a comprehensive overview of the evidence for <sup>18</sup>F-prostate specific membrane antigen (PSMA) PET/CT in the staging of high-risk prostate cancer and restaging after biochemical recurrence. An overview of reviews was performed and reported in line with the preferred reporting items for overview of reviews (PRIOR) statement and synthesis without meta-analysis (SWiM) reporting guidelines. A comprehensive database and grey literature search were conducted up to July 18, 2023. Systematic reviews were assessed using the risk of bias in systematic reviews (ROBIS) tool. The certainty of the evidence was assessed using grading of recommendations, assessment, development and evaluations (GRADE). 11 systematic reviews were identified; 10 were at high or unclear risk of bias. Evidence reported on a per-patient, per-lymph node, and per-lesion basis for sensitivity, specificity and overall accuracy was identified. There was a lack of data on dose, adverse events and evidence directly comparing <sup>18</sup>F-PSMA PET/CT to other imaging modalities. Evidence with moderate to very low certainty indicated high sensitivity, specificity and accuracy of <sup>18</sup>F-PSMA PET/CT in patients with high-risk prostate cancer and biochemical recurrence. There was considerably lower certainty evidence and greater variability in effect estimates for outcomes for the combined intermediate/high-risk cohort. While evidence gaps remain for some outcomes, and most systematic reviews were at high or unclear risk of bias, the current evidence base is broadly supportive of <sup>18</sup>F-PSMA PET/CT imaging in the staging and restaging of patients with high-risk prostate cancer and biochemical recurrence.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 680-700"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437431","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}
Pub Date : 2025-09-01Epub Date: 2025-07-29DOI: 10.1053/j.semnuclmed.2025.07.004
Kirsten Bouchelouche, M. Michael Sathekge
{"title":"Letter from the Editors","authors":"Kirsten Bouchelouche, M. Michael Sathekge","doi":"10.1053/j.semnuclmed.2025.07.004","DOIUrl":"10.1053/j.semnuclmed.2025.07.004","url":null,"abstract":"","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 645-647"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723310","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}
Pub Date : 2025-09-01Epub Date: 2025-07-22DOI: 10.1053/j.semnuclmed.2025.06.013
Honest Ndlovu , Ismaheel O. Lawal , Kgomotso M.G. Mokoala , Sipho Mdanda , Mike M. Sathekge
The diagnosis of infection is crucial in-patient survival, prevention of prolonged hospitalization and undue morbidity and mortality. This can be achieved using various tools target at the specific microbes or the host immune response components. The most useful tool will be one that diagnoses the specific causative microbe by being able to distinguish sterile inflammation from infection which by itself causes inflammation. This allows timeous institution of the appropriate and effective antimicrobial therapy, effectively reducing the incidence of antimicrobial resistance. Current standard of care diagnostic tools such as inflammatory markers, culture, morphological imaging and molecular imaging tools has specific shortcomings which necessities enlist other tools to complement them. Various targets for infection imaging have been explored and demonstrated variable utilities in the preclinical or clinical settings. This review will discuss the relevant targets in bacteria, fungi and viruses and delve into the promising or novel molecular imaging tools.
{"title":"New Promising Targets for Imaging in Infection","authors":"Honest Ndlovu , Ismaheel O. Lawal , Kgomotso M.G. Mokoala , Sipho Mdanda , Mike M. Sathekge","doi":"10.1053/j.semnuclmed.2025.06.013","DOIUrl":"10.1053/j.semnuclmed.2025.06.013","url":null,"abstract":"<div><div>The diagnosis of infection is crucial in-patient survival, prevention of prolonged hospitalization and undue morbidity and mortality. This can be achieved using various tools target at the specific microbes or the host immune response components. The most useful tool will be one that diagnoses the specific causative microbe by being able to distinguish sterile inflammation from infection which by itself causes inflammation. This allows timeous institution of the appropriate and effective antimicrobial therapy, effectively reducing the incidence of antimicrobial resistance. Current standard of care diagnostic tools such as inflammatory markers, culture, morphological imaging and molecular imaging tools has specific shortcomings which necessities enlist other tools to complement them. Various targets for infection imaging have been explored and demonstrated variable utilities in the preclinical or clinical settings. This review will discuss the relevant targets in bacteria, fungi and viruses and delve into the promising or novel molecular imaging tools.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 804-811"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699388","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}
Neuroendocrine neoplasms (NENs) represent a diverse group of tumors originating from neuroendocrine cells, characterized by their unique biological behavior and clinical manifestations. The incidence of neuroendocrine tumors (NETs) has been rising, necessitating effective diagnostic and therapeutic strategies. Molecular imaging, particularly through techniques such as PET and SPECT, plays a pivotal role in the management of NETs. This review highlights the significance of somatostatin receptor imaging in the initial diagnostic work-up, staging, and treatment planning for NETs, emphasizing the utility of radiopharmaceuticals like [68Ga]Ga-DOTATATE and [68Ga]Ga-DOTA-LM3. These agents demonstrate high sensitivity and specificity, allowing for accurate delineation of disease extent and identification of occult primary tumors. Furthermore, the review discusses the emerging role of nonsomatostatin receptor targets, such as glucose metabolism and fibroblast activation protein, in enhancing the diagnostic capabilities of molecular imaging. The integration of advanced imaging modalities, including dual-tracer approaches, is explored for their potential to refine therapeutic strategies and improve patient outcomes. As the field of molecular imaging continues to evolve, ongoing research and clinical trials are essential to validate the efficacy and safety of novel imaging agents and techniques, ultimately enhancing the management of patients with neuroendocrine tumors.
{"title":"Targets for Molecular Imaging of Neuroendocrine Tumors (NETs): An Overview and Update","authors":"Esmail Jafari , Majid Assadi , Meysam Nasiri , Hojjat Ahmadzadehfar","doi":"10.1053/j.semnuclmed.2025.04.003","DOIUrl":"10.1053/j.semnuclmed.2025.04.003","url":null,"abstract":"<div><div>Neuroendocrine neoplasms (NENs) represent a diverse group of tumors originating from neuroendocrine cells, characterized by their unique biological behavior and clinical manifestations. The incidence of neuroendocrine tumors (NETs) has been rising, necessitating effective diagnostic and therapeutic strategies. Molecular imaging, particularly through techniques such as PET and SPECT, plays a pivotal role in the management of NETs. This review highlights the significance of somatostatin receptor imaging in the initial diagnostic work-up, staging, and treatment planning for NETs, emphasizing the utility of radiopharmaceuticals like [<sup>68</sup>Ga]Ga-DOTATATE and [<sup>68</sup>Ga]Ga-DOTA-LM3. These agents demonstrate high sensitivity and specificity, allowing for accurate delineation of disease extent and identification of occult primary tumors. Furthermore, the review discusses the emerging role of nonsomatostatin receptor targets, such as glucose metabolism and fibroblast activation protein, in enhancing the diagnostic capabilities of molecular imaging. The integration of advanced imaging modalities, including dual-tracer approaches, is explored for their potential to refine therapeutic strategies and improve patient outcomes. As the field of molecular imaging continues to evolve, ongoing research and clinical trials are essential to validate the efficacy and safety of novel imaging agents and techniques, ultimately enhancing the management of patients with neuroendocrine tumors.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 740-753"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182911","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}
Pub Date : 2025-09-01Epub Date: 2025-05-21DOI: 10.1053/j.semnuclmed.2025.04.006
Zhaoguo Lin , Pawel Rasinski , Ted Nilsson , Maria Holstensson , Yangmeihui Song , August Blomgren , Warissara Jutidamrongphan , Kalyani Pandya , Jimin Hong , Axel Rominger , Kuangyu Shi , Rimma Axelsson , Xiaoli Lan , Robert Seifert
Fibroblast activation protein (FAP) is a type II transmembrane serine protease that is highly expressed in cancer-associated fibroblasts (CAFs) but absent in quiescent fibroblasts. Its overexpression is associated with poor prognosis in various cancers and contributes to treatment resistance. In recent years, radiolabeled FAP inhibitors (FAPI) for PET imaging have shown promising clinical value across a range of cancers. Gastrointestinal (GI) malignancies, which often exhibit a desmoplastic reaction with a high density of FAP-expressing CAFs, are particularly well-suited for FAPI PET. Given the limitations of [18F]FDG PET in GI cancers, such as low sensitivity in certain histological subtypes and high physiological background uptake, FAPI PET is expected to serve as a complementary method, potentially enhancing both diagnostic accuracy and treatment guidance. This review provides a comprehensive comparison of the clinical applications of FAPI PET and [18F]FDG PET in various GI cancers, including their value in diagnosis, staging, and treatment guidance. Additionally, this review summarizes studies on the expanding role of FAPI PET, including its use in assessing treatment response and predicting prognosis, aiming to provide insights into its potential contribution to the improved management of GI malignancies.
{"title":"FAPI PET Versus FDG PET/CT in Gastrointestinal Cancers: An Overview","authors":"Zhaoguo Lin , Pawel Rasinski , Ted Nilsson , Maria Holstensson , Yangmeihui Song , August Blomgren , Warissara Jutidamrongphan , Kalyani Pandya , Jimin Hong , Axel Rominger , Kuangyu Shi , Rimma Axelsson , Xiaoli Lan , Robert Seifert","doi":"10.1053/j.semnuclmed.2025.04.006","DOIUrl":"10.1053/j.semnuclmed.2025.04.006","url":null,"abstract":"<div><div>Fibroblast activation protein (FAP) is a type II transmembrane serine protease that is highly expressed in cancer-associated fibroblasts (CAFs) but absent in quiescent fibroblasts. Its overexpression is associated with poor prognosis in various cancers and contributes to treatment resistance. In recent years, radiolabeled FAP inhibitors (FAPI) for PET imaging have shown promising clinical value across a range of cancers. Gastrointestinal (GI) malignancies, which often exhibit a desmoplastic reaction with a high density of FAP-expressing CAFs, are particularly well-suited for FAPI PET. Given the limitations of [<sup>18</sup>F]FDG PET in GI cancers, such as low sensitivity in certain histological subtypes and high physiological background uptake, FAPI PET is expected to serve as a complementary method, potentially enhancing both diagnostic accuracy and treatment guidance. This review provides a comprehensive comparison of the clinical applications of FAPI PET and [<sup>18</sup>F]FDG PET in various GI cancers, including their value in diagnosis, staging, and treatment guidance. Additionally, this review summarizes studies on the expanding role of FAPI PET, including its use in assessing treatment response and predicting prognosis, aiming to provide insights into its potential contribution to the improved management of GI malignancies.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 710-723"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120739","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}
Pub Date : 2025-09-01Epub Date: 2025-02-24DOI: 10.1053/j.semnuclmed.2025.01.005
Geoffrey M. Currie , Eric M. Rohren
While theranostics has transformed the precision medicine landscape over the last decade, there is scope for the development of true theranostic pairs, e.g. diagnostic and therapeutic partners in which any physical, chemical, and biological differences are negligible to in vivo application. Although simple to state in theory, there are, in fact, limited options exhibiting optimal physical characteristics and wholly shared elements.
Further compounding real-world application of the traditional theranostic method are additional barriers. The use of PET/CT as the cornerstone of the diagnostic pair in theranostics creates inequity of access and opportunity based on socioeconomic and geographic factors, and the growing demand for both 68Ga and 177Lu is straining production capabilities globally. Improving access to theranostics globally will require novel thinking and infrastructure investment to ensure that patients of all economic and social backgrounds have access to this transformative technology.
An approach which is underdeveloped, but which may address gaps in health inequities and improve outcomes, is the application of the widely available generator-produced 99mTc for imaging and 188Re for therapy. Despite favourable and near identical radiochemistry, the search for the next generation of theranostic radionuclide pairs seldom references technetium or rhenium radionuclides. Advances in SPECT/CT instrumentation and radiochemistry provide an opportunity to deliver theranostics to communities not serviced by PET-based theranostics. The 188Re and 99mTc supply by daily elution of a generator affords significant convenience, flexibility and delayed biomolecule imaging. Low abundance gamma emissions of 188Re allow serial imaging and dosimetry calculations. 99mTc / 188Re theranostics could address inequity in access and opportunity to cutting edge theranostics.
{"title":"Potential of Technetium and Rhenium Theranostics","authors":"Geoffrey M. Currie , Eric M. Rohren","doi":"10.1053/j.semnuclmed.2025.01.005","DOIUrl":"10.1053/j.semnuclmed.2025.01.005","url":null,"abstract":"<div><div>While theranostics has transformed the precision medicine landscape over the last decade, there is scope for the development of true theranostic pairs, e.g. diagnostic and therapeutic partners in which any physical, chemical, and biological differences are negligible to <em>in vivo</em> application. Although simple to state in theory, there are, in fact, limited options exhibiting optimal physical characteristics and wholly shared elements.</div><div>Further compounding real-world application of the traditional theranostic method are additional barriers. The use of PET/CT as the cornerstone of the diagnostic pair in theranostics creates inequity of access and opportunity based on socioeconomic and geographic factors, and the growing demand for both <sup>68</sup>Ga and <sup>177</sup>Lu is straining production capabilities globally. Improving access to theranostics globally will require novel thinking and infrastructure investment to ensure that patients of all economic and social backgrounds have access to this transformative technology.</div><div>An approach which is underdeveloped, but which may address gaps in health inequities and improve outcomes, is the application of the widely available generator-produced <sup>99m</sup>Tc for imaging and <sup>188</sup>Re for therapy. Despite favourable and near identical radiochemistry, the search for the next generation of theranostic radionuclide pairs seldom references technetium or rhenium radionuclides. Advances in SPECT/CT instrumentation and radiochemistry provide an opportunity to deliver theranostics to communities not serviced by PET-based theranostics. The <sup>188</sup>Re and <sup>99m</sup>Tc supply by daily elution of a generator affords significant convenience, flexibility and delayed biomolecule imaging. Low abundance gamma emissions of <sup>188</sup>Re allow serial imaging and dosimetry calculations. <sup>99m</sup>Tc / <sup>188</sup>Re theranostics could address inequity in access and opportunity to cutting edge theranostics.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 829-840"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503570","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}
Pub Date : 2025-09-01Epub Date: 2025-06-07DOI: 10.1053/j.semnuclmed.2025.05.004
Yu-Jie Yang , Yi-Xin Zhao , Xin-Yi Li , Chuantao Zuo
In recent years, the neuroimaging biomarkers for Parkinson’s disease (PD) has advanced rapidly, targeting to the key pathological mechanisms such as α-synuclein (α-syn) aggregation, neuroinflammation, mitochondrial dysfunction and brain clearance. This review summarized the novel imaging targets and their clinical practice in human studies. The presynaptic dopamine transporters and 18F-Fluorodeoxyglucose positron emission tomography (PET) have been characterized as established biomarkers in PD. Furthermore, as the key pathogenic protein in PD, α-syn aggregation forming Lewy bodies could drive the neuronal degeneration, making the α-syn-targeted PET imaging a critical focus in PD research. Other co-pathologies, including amyloid-β and tau protein, were also concluded for their clinical implications in PD. Additionally, the PET imaging targets for neuroinflammatory mechanisms, including mitochondrial dysfunction, microglial and astrocyte activation, hold promise for further investigation. Finally, the radiotracers detecting disruptions of blood-brain barrier and glymphatic system would also represent as therapeutic opportunities. In conclusion, the vigorous development of novel imaging biomarkers in PD will refine the diagnostic frameworks, promoting for the future disease-modifying therapies.
{"title":"New Targets for Positron Emission Tomography Imaging in Parkinson´s Disease","authors":"Yu-Jie Yang , Yi-Xin Zhao , Xin-Yi Li , Chuantao Zuo","doi":"10.1053/j.semnuclmed.2025.05.004","DOIUrl":"10.1053/j.semnuclmed.2025.05.004","url":null,"abstract":"<div><div>In recent years, the neuroimaging biomarkers for Parkinson’s disease (PD) has advanced rapidly, targeting to the key pathological mechanisms such as α-synuclein (α-syn) aggregation, neuroinflammation, mitochondrial dysfunction and brain clearance. This review summarized the novel imaging targets and their clinical practice in human studies. The presynaptic dopamine transporters and <sup>18</sup>F-Fluorodeoxyglucose positron emission tomography (PET) have been characterized as established biomarkers in PD. Furthermore, as the key pathogenic protein in PD, α-syn aggregation forming Lewy bodies could drive the neuronal degeneration, making the α-syn-targeted PET imaging a critical focus in PD research. Other co-pathologies, including amyloid-β and tau protein, were also concluded for their clinical implications in PD. Additionally, the PET imaging targets for neuroinflammatory mechanisms, including mitochondrial dysfunction, microglial and astrocyte activation, hold promise for further investigation. Finally, the radiotracers detecting disruptions of blood-brain barrier and glymphatic system would also represent as therapeutic opportunities. In conclusion, the vigorous development of novel imaging biomarkers in PD will refine the diagnostic frameworks, promoting for the future disease-modifying therapies.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 795-803"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249467","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}
Pub Date : 2025-09-01Epub Date: 2025-06-23DOI: 10.1053/j.semnuclmed.2025.05.006
Mia Ståhle , Cristina Popescu , Christoph Rischpler , Han Zhang , Samia Massalha , Leonor Lopes , Axel Rominger , Federico Caobelli
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, driven by complex and dynamic molecular processes such as inflammation, fibrosis, metabolic dysregulation, thrombosis, and vascular remodeling. While conventional imaging techniques provide valuable anatomical and functional information, they fail to capture these underlying pathophysiological mechanisms at the molecular level. Molecular imaging, particularly with PET and SPECT, offers the potential to noninvasively visualize and quantify these processes, enabling earlier diagnosis, better risk stratification, and more precise treatment guidance. Despite substantial progress in clinical cardiology, there is a growing need for novel radiotracers that can target key disease-driving mechanisms beyond traditional perfusion or viability imaging. Emerging radiopharmaceuticals now enable the assessment of myocardial fibrosis (e.g., collagen-targeted and MMP-targeted tracers), cardiomyocyte stress responses (e.g., oxidative stress, unfolded protein response, endothelin signaling), and metabolic alterations (e.g., fatty acid, ketone, and glucose metabolism). Additionally, new tracers are being developed for thrombosis, vascular inflammation, plaque instability, and even for innovative targets such as cellular senescence and gut-derived inflammatory pathways. These developments reflect a paradigm shift towards imaging-driven phenotyping of cardiovascular disease. This review provides a comprehensive overview of the latest advances in molecular imaging tracers for cardiovascular applications, with a focus on their biological rationale, preclinical and clinical evidence, and translational challenges. We categorize tracers by their mechanistic targets and highlight their potential for integration into precision cardiology.
{"title":"New Promising Targets for Imaging in Cardiovascular Diseases","authors":"Mia Ståhle , Cristina Popescu , Christoph Rischpler , Han Zhang , Samia Massalha , Leonor Lopes , Axel Rominger , Federico Caobelli","doi":"10.1053/j.semnuclmed.2025.05.006","DOIUrl":"10.1053/j.semnuclmed.2025.05.006","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, driven by complex and dynamic molecular processes such as inflammation, fibrosis, metabolic dysregulation, thrombosis, and vascular remodeling. While conventional imaging techniques provide valuable anatomical and functional information, they fail to capture these underlying pathophysiological mechanisms at the molecular level. Molecular imaging, particularly with PET and SPECT, offers the potential to noninvasively visualize and quantify these processes, enabling earlier diagnosis, better risk stratification, and more precise treatment guidance. Despite substantial progress in clinical cardiology, there is a growing need for novel radiotracers that can target key disease-driving mechanisms beyond traditional perfusion or viability imaging. Emerging radiopharmaceuticals now enable the assessment of myocardial fibrosis (e.g., collagen-targeted and MMP-targeted tracers), cardiomyocyte stress responses (e.g., oxidative stress, unfolded protein response, endothelin signaling), and metabolic alterations (e.g., fatty acid, ketone, and glucose metabolism). Additionally, new tracers are being developed for thrombosis, vascular inflammation, plaque instability, and even for innovative targets such as cellular senescence and gut-derived inflammatory pathways. These developments reflect a paradigm shift towards imaging-driven phenotyping of cardiovascular disease. This review provides a comprehensive overview of the latest advances in molecular imaging tracers for cardiovascular applications, with a focus on their biological rationale, preclinical and clinical evidence, and translational challenges. We categorize tracers by their mechanistic targets and highlight their potential for integration into precision cardiology.</div></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":"55 5","pages":"Pages 812-828"},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485772","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}
Pub Date : 2025-09-01Epub Date: 2025-01-24DOI: 10.1053/j.semnuclmed.2025.01.001
Nasibeh Mohseninia , Roya Eisazadeh , Seyed Ali Mirshahvalad , Nazanin Zamani-Siahkali , Anton Amadeus Hörmann , Christian Pirich , Andrei Iagaru , Mohsen Beheshti
Gastrin-releasing peptide receptor (GRPR), overexpressed in various cancers, is a promising target for positron emission tomography (PET). This systematic review investigated the diagnostic value of GRPR-targeted PET imaging in oncology. A systematic search was conducted on major medical databases until May 23, 2024. Keywords were modified to include clinical original studies on GRPR-targeted PET in cancer patients. Out of 1624 searched studies initially, 107 were eligible for the full-text review. Overall, data from 38 studies met inclusion criteria, investigating GRPR-targeting radiotracers in breast cancer, prostate cancer, gastrointestinal stromal tumours (GIST) and gliomas (including optic pathway glioma and glioblastoma multiforme). In breast cancer, GRPR-targeted PET effectively detected primary tumours and metastases, particularly in estrogen receptor (ER)-positive patients, and predicted treatment response. In prostate cancer, high sensitivity (up to 88%) and specificity (up to 90%) for detecting primary tumours were observed, providing added value when combined with magnetic resonance imaging (MRI). In biochemical recurrence, sites of prostate cancer were identified even at PSA levels below 0.5ng/dL. Compared with PSMA PET, GRPR-targeted PET showed comparable or superior detection rates. Considering GIST, GRPR-targeted PET imaging proved to be a valuable diagnostic tool, particularly when [18F] FDG PET results were inconclusive. Regarding gliomas, GRPR-targeted PET achieved a 100% detection rate (MRI reference), aiding localization, preoperative planning, and differentiation between recurrence and malignant transformation. GRPR-targeted PET shows promise in improving cancer diagnostics, particularly in ER-positive breast cancer, prostate cancer, and gliomas, and may enhance clinical decision-making.
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