{"title":"Correction to: 68Ga-FAPI and 18F-FDG PET/CT for predicting pathologic response and progression-free survival in locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy","authors":"Jiaon Dai, Yuheng Zou, Hui Wang, Hexiao Huang, Lixiang Yang, Bingwen Zou, Rong Tian","doi":"10.1007/s00259-026-07767-9","DOIUrl":"https://doi.org/10.1007/s00259-026-07767-9","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"102 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1007/s00259-025-07749-3
Dilara Denizmen Zorba, Duygu Has Simsek, Yasemin Sanli, Muhammet Ibrahim Karacam, Omer Naci Ergin, Arif Atahan Cagatay, Fikret Buyukkaya, Serkan Kuyumcu
Purpose Chronic bone and soft tissue infections pose a diagnostic challenge, as conventional imaging techniques often show limited sensitivity and specificity. Given that CXCR4 chemokine receptors are expressed on lymphocytes, key mediators of chronic inflammatory response, we hypothesized that CXCR4-targeted imaging may offer enhanced diagnostic accuracy. Accordingly, this study aimed to evaluate the diagnostic performance of [ 68 Ga]Ga-Pentixafor PET/CT in comparison with conventional 3-phase bone scintigraphy and [ 99m Tc]Tc-HMPAO-labelled leucocyte scintigraphy in patients with suspected chronic bone and soft tissue infections. Methods In this retrospective single-centre study, we included patients who underwent both conventional scintigraphic imaging and [ 68 Ga]Ga-Pentixafor PET/CT. Asymptomatic prostheses, orthopaedic implants, and diabetic foot regions within the same cohort served as controls. Two nuclear medicine specialists, blinded to patient data, evaluated imaging findings in consensus visually and quantitatively. Final diagnoses were confirmed by microbiological culture and/or histopathology for infected sites, and by clinical and radiological follow-up for non-infected control sites. Results A total of 20 patients with 25 suspected infectious foci and 14 control sites were evaluated. Of the 25 sites, 21 were confirmed to be infected; no infections were observed in the control sites. Scintigraphy correctly identified 19 infection sites (sensitivity: 90%, specificity: 83%), while [ 68 Ga]Ga-Pentixafor PET/CT was positive in all 21 infection sites, but demonstrated two false-positives (sensitivity: 100%, specificity: 89%). PET/CT showed higher overall accuracy (95% vs. 87%), although this difference did not reach statistical significance ( p = 0.07). Conclusion [ 68 Ga]Ga-Pentixafor PET/CT was accurate in detecting BSTIs, suggesting potential utility as a single-scan imaging approach. These results align with findings from limited prior studies and underscore the need for validation in larger cohorts.
{"title":"Evaluating chronic bone and soft tissue infections with [68Ga]Ga-Pentixafor PET/CT: a head-to-head comparison with scintigraphy","authors":"Dilara Denizmen Zorba, Duygu Has Simsek, Yasemin Sanli, Muhammet Ibrahim Karacam, Omer Naci Ergin, Arif Atahan Cagatay, Fikret Buyukkaya, Serkan Kuyumcu","doi":"10.1007/s00259-025-07749-3","DOIUrl":"https://doi.org/10.1007/s00259-025-07749-3","url":null,"abstract":"Purpose Chronic bone and soft tissue infections pose a diagnostic challenge, as conventional imaging techniques often show limited sensitivity and specificity. Given that CXCR4 chemokine receptors are expressed on lymphocytes, key mediators of chronic inflammatory response, we hypothesized that CXCR4-targeted imaging may offer enhanced diagnostic accuracy. Accordingly, this study aimed to evaluate the diagnostic performance of [ <jats:sup>68</jats:sup> Ga]Ga-Pentixafor PET/CT in comparison with conventional 3-phase bone scintigraphy and [ <jats:sup>99m</jats:sup> Tc]Tc-HMPAO-labelled leucocyte scintigraphy in patients with suspected chronic bone and soft tissue infections. Methods In this retrospective single-centre study, we included patients who underwent both conventional scintigraphic imaging and [ <jats:sup>68</jats:sup> Ga]Ga-Pentixafor PET/CT. Asymptomatic prostheses, orthopaedic implants, and diabetic foot regions within the same cohort served as controls. Two nuclear medicine specialists, blinded to patient data, evaluated imaging findings in consensus visually and quantitatively. Final diagnoses were confirmed by microbiological culture and/or histopathology for infected sites, and by clinical and radiological follow-up for non-infected control sites. Results A total of 20 patients with 25 suspected infectious foci and 14 control sites were evaluated. Of the 25 sites, 21 were confirmed to be infected; no infections were observed in the control sites. Scintigraphy correctly identified 19 infection sites (sensitivity: 90%, specificity: 83%), while [ <jats:sup>68</jats:sup> Ga]Ga-Pentixafor PET/CT was positive in all 21 infection sites, but demonstrated two false-positives (sensitivity: 100%, specificity: 89%). PET/CT showed higher overall accuracy (95% vs. 87%), although this difference did not reach statistical significance ( <jats:italic>p</jats:italic> = 0.07). Conclusion [ <jats:sup>68</jats:sup> Ga]Ga-Pentixafor PET/CT was accurate in detecting BSTIs, suggesting potential utility as a single-scan imaging approach. These results align with findings from limited prior studies and underscore the need for validation in larger cohorts.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"397 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PURPOSEImpaired glymphatic function is considered an important characteristic of cognitive decline, but the role of tau pathology as a mediator remains unclear. This study investigated whether tau burden mediates the association between diffusion tensor image analysis along the perivascular space (DTI-ALPS) and cognitive impairment or brain atrophy. Also, we explored whether DTI-ALPS index predicts longitudinal cognitive deterioration over time.METHODSWe included 144 individuals with mild cognitive impairment (MCI), Alzheimer's disease dementia (ADD), and other dementia, or normal cognition. All participants underwent 3.0-Tesla MRI, 18F-MK6240 and 18F-Flutemetamol PET scans, APOE genotyping, and comprehensive neuropsychological assessments. Among these, 101 were followed longitudinally for two years. Mediation analyses within a causal framework were used to investigate whether tau burden mediated the association between DTI-ALPS index and cognition function and structural MRI measures. Longitudinal associations were tested using linear mixed-effects models.RESULTSDTI-ALPS index was significantly lower in cognitively impaired individuals compared to cognitively normal (CN) participants. Lower DTI-ALPS index was associated with higher tau burden and worse cognitive function. Tau burden was also inversely associated with cognition. Mediation analysis indicated that tau burden accounted for approximately 21-27% of the association between DTI-ALPS and cognition. Longitudinal analysis showed baseline lower DTI-ALPS index also predicted faster longitudinal cognitive decline.CONCLUSIONOur findings suggest that the DTI-ALPS index is an indirect marker of glymphatic dysfunction associated with tau accumulation and cognitive decline. Tau pathology may partially link compromised glymphatic clearance to cognitive impairment.
{"title":"Tau PET imaging as a mediator between glymphatic dysfunction and cognitive decline: a cross-sectional and longitudinal study.","authors":"Juyeon Ko,Gayeong Son,Ha Eun Seo,Jaelim Cho,Jae-Yoon Kim,Sang-Yoon Lee,Daegyeom Kim,ShinEui Park,Kee Hyung Park,Samuel N Lockhart,Dong-Hyun Kim,Young Noh","doi":"10.1007/s00259-025-07756-4","DOIUrl":"https://doi.org/10.1007/s00259-025-07756-4","url":null,"abstract":"PURPOSEImpaired glymphatic function is considered an important characteristic of cognitive decline, but the role of tau pathology as a mediator remains unclear. This study investigated whether tau burden mediates the association between diffusion tensor image analysis along the perivascular space (DTI-ALPS) and cognitive impairment or brain atrophy. Also, we explored whether DTI-ALPS index predicts longitudinal cognitive deterioration over time.METHODSWe included 144 individuals with mild cognitive impairment (MCI), Alzheimer's disease dementia (ADD), and other dementia, or normal cognition. All participants underwent 3.0-Tesla MRI, 18F-MK6240 and 18F-Flutemetamol PET scans, APOE genotyping, and comprehensive neuropsychological assessments. Among these, 101 were followed longitudinally for two years. Mediation analyses within a causal framework were used to investigate whether tau burden mediated the association between DTI-ALPS index and cognition function and structural MRI measures. Longitudinal associations were tested using linear mixed-effects models.RESULTSDTI-ALPS index was significantly lower in cognitively impaired individuals compared to cognitively normal (CN) participants. Lower DTI-ALPS index was associated with higher tau burden and worse cognitive function. Tau burden was also inversely associated with cognition. Mediation analysis indicated that tau burden accounted for approximately 21-27% of the association between DTI-ALPS and cognition. Longitudinal analysis showed baseline lower DTI-ALPS index also predicted faster longitudinal cognitive decline.CONCLUSIONOur findings suggest that the DTI-ALPS index is an indirect marker of glymphatic dysfunction associated with tau accumulation and cognitive decline. Tau pathology may partially link compromised glymphatic clearance to cognitive impairment.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"41 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1007/s00259-026-07764-y
Tan Hui, Zhiqun Mao
{"title":"\"Tiger man sign\" in sarcoid myopathy.","authors":"Tan Hui, Zhiqun Mao","doi":"10.1007/s00259-026-07764-y","DOIUrl":"https://doi.org/10.1007/s00259-026-07764-y","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1007/s00259-026-07772-y
Wolfram A Bosbach,Radi Saiyed Alsheikh,Nasir Gözlügöl,Federico Caobelli,Robert Seifert,Clemens Mingels,Mohamed Shelan,Dilara Akhoundova,Berna C Özdemir,Jörg Beyer,Paul Cumming,Axel Rominger,Ali Afshar-Oromieh
INTRODUCTIONWe investigated whether prompt changes in prostate-specific-antigen (PSA) levels within two days after the first cycle of prostate-specific-membrane-antigen radioligand therapy (PSMA-RLT) with [177Lu]Lu-PSMA-617 predicted treatment response and mean survival.METHODSIn a retrospective study of 76 metastatic castration resistant prostate cancer (mCRPC) patients, we evaluated pretreatment PSA-values and their relative changes in PSA (dPSA) two days later. We tested for correlations between dPSA with long-term biochemical response (BCR) to treatment, using a priori criteria for relevant PSA decrease (dPSA < -10%), stable PSA (-10% ≤ dPSA ≤ + 10%) and relevant PSA increase (dPSA > 10%), along with evaluation of biochemical therapy outcome according to the Prostate-Cancer-Working-Group (PCWG3).RESULTSTwo days after the first [177Lu]Lu-PSMA-617 cycle, 32 (42%) of the patientsshowed PSA decrease, of whom 19 (59%) had experienced a partial response according toPCWG3 criteria. Of the 37 patients with stable PSA, 17 (46%) showed partial response totreatment according to PCWG3 criteria. Among the seven patients with PSA increase, three(43%) showed partial response. Pearson correlation analysis showed statistically significantcorrelations between dPSA on day 2 and relative Nadir for the first two treatment cycles.Patients with PSA decrease or stable PSA compared to those with an increase of PSA two daysafter cycle 1 lived longer on average (399, 405 and 225 days, respectively).CONCLUSIONCompared to those with increased PSA levels, patients with decreased or stable PSA levels two days after the first [177Lu]Lu-PSMA-617 RLT cycle were more likely to have favorable biochemical response according to PCWG3 criteria and presented with a longer overall survival.
{"title":"Prompt PSA changes as a prognostic marker for response to PSMA-radioligand therapy.","authors":"Wolfram A Bosbach,Radi Saiyed Alsheikh,Nasir Gözlügöl,Federico Caobelli,Robert Seifert,Clemens Mingels,Mohamed Shelan,Dilara Akhoundova,Berna C Özdemir,Jörg Beyer,Paul Cumming,Axel Rominger,Ali Afshar-Oromieh","doi":"10.1007/s00259-026-07772-y","DOIUrl":"https://doi.org/10.1007/s00259-026-07772-y","url":null,"abstract":"INTRODUCTIONWe investigated whether prompt changes in prostate-specific-antigen (PSA) levels within two days after the first cycle of prostate-specific-membrane-antigen radioligand therapy (PSMA-RLT) with [177Lu]Lu-PSMA-617 predicted treatment response and mean survival.METHODSIn a retrospective study of 76 metastatic castration resistant prostate cancer (mCRPC) patients, we evaluated pretreatment PSA-values and their relative changes in PSA (dPSA) two days later. We tested for correlations between dPSA with long-term biochemical response (BCR) to treatment, using a priori criteria for relevant PSA decrease (dPSA < -10%), stable PSA (-10% ≤ dPSA ≤ + 10%) and relevant PSA increase (dPSA > 10%), along with evaluation of biochemical therapy outcome according to the Prostate-Cancer-Working-Group (PCWG3).RESULTSTwo days after the first [177Lu]Lu-PSMA-617 cycle, 32 (42%) of the patientsshowed PSA decrease, of whom 19 (59%) had experienced a partial response according toPCWG3 criteria. Of the 37 patients with stable PSA, 17 (46%) showed partial response totreatment according to PCWG3 criteria. Among the seven patients with PSA increase, three(43%) showed partial response. Pearson correlation analysis showed statistically significantcorrelations between dPSA on day 2 and relative Nadir for the first two treatment cycles.Patients with PSA decrease or stable PSA compared to those with an increase of PSA two daysafter cycle 1 lived longer on average (399, 405 and 225 days, respectively).CONCLUSIONCompared to those with increased PSA levels, patients with decreased or stable PSA levels two days after the first [177Lu]Lu-PSMA-617 RLT cycle were more likely to have favorable biochemical response according to PCWG3 criteria and presented with a longer overall survival.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"6 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PURPOSEThis review examines Marine-Lenhart syndrome (MLS), an uncommon thyroid disorder that combines Graves' disease with autonomously functioning thyroid nodules (AFTNs) and demonstrates why nuclear medicine imaging is essential for accurate diagnosis and treatment planning.METHODSWe reviewed case reports and case series published over the past three decades and analyzed clinical presentation, diagnostic approaches, prevalence rates, disease mechanisms, and treatment outcomes of MLS.RESULTSThis relatively rare syndrome occurs in approximately 0.8-4.3% of patients with Graves' disease, though rates vary depending on the diagnostic criteria and imaging methods used. It presents a diagnostic challenge because AFTNs often remain suppressed and appear "cold" on initial scans, only becoming visible after treatment - the characteristic "unmasking effect". Thyroid scintigraphy with either 99mTc-pertechnetate or 123I provides functional information that structural imaging cannot show. Treatment differs from standard Graves' disease management as MLS requires higher radioiodine activities because nodules may escape radiation damage, and patients may need radioiodine re-ablation. Type 3 MLS, which includes cold nodules, requires careful cancer risk evaluation with ultrasound and fine-needle aspiration when appropriate.CONCLUSIONNuclear medicine imaging is crucial for MLS diagnosis and treatment planning. Functional imaging identifies AFTNs, guides appropriate radioiodine treatment, and prevents treatment failure. Routine thyroid scintigraphy is recommended in all patients with hyperthyroidism and thyroid nodules before starting therapy.
{"title":"Marine-Lenhart syndrome: why nuclear medicine imaging remains essential for diagnosis and treatment.","authors":"Petra Petranović Ovčariček,Rosaria Maddalena Ruggeri,Alfredo Campennì,Isabella Corrêa Chaves Nunes,Daria Maccora,Murat Tuncel,Luca Giovanella","doi":"10.1007/s00259-025-07751-9","DOIUrl":"https://doi.org/10.1007/s00259-025-07751-9","url":null,"abstract":"PURPOSEThis review examines Marine-Lenhart syndrome (MLS), an uncommon thyroid disorder that combines Graves' disease with autonomously functioning thyroid nodules (AFTNs) and demonstrates why nuclear medicine imaging is essential for accurate diagnosis and treatment planning.METHODSWe reviewed case reports and case series published over the past three decades and analyzed clinical presentation, diagnostic approaches, prevalence rates, disease mechanisms, and treatment outcomes of MLS.RESULTSThis relatively rare syndrome occurs in approximately 0.8-4.3% of patients with Graves' disease, though rates vary depending on the diagnostic criteria and imaging methods used. It presents a diagnostic challenge because AFTNs often remain suppressed and appear \"cold\" on initial scans, only becoming visible after treatment - the characteristic \"unmasking effect\". Thyroid scintigraphy with either 99mTc-pertechnetate or 123I provides functional information that structural imaging cannot show. Treatment differs from standard Graves' disease management as MLS requires higher radioiodine activities because nodules may escape radiation damage, and patients may need radioiodine re-ablation. Type 3 MLS, which includes cold nodules, requires careful cancer risk evaluation with ultrasound and fine-needle aspiration when appropriate.CONCLUSIONNuclear medicine imaging is crucial for MLS diagnosis and treatment planning. Functional imaging identifies AFTNs, guides appropriate radioiodine treatment, and prevents treatment failure. Routine thyroid scintigraphy is recommended in all patients with hyperthyroidism and thyroid nodules before starting therapy.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"29 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1007/s00259-026-07760-2
Enio Barci,Maximilian J Mair,Jonas Reis,Katharina Müller,Jera Isakaj,Ergi Istrefi,Isabelle von Polenz,Sophie C Siegmund,Lena Kaiser,Matthias Preusser,Christian Schichor,Niklas Thon,Patrick Harter,Louisa von Baumgarten,Robert Forbrig,Nathalie L Albert
{"title":"Characteristics of [18F]FET PET and MRI in isocitrate dehydrogenase (IDH)-mutant gliomas diagnosed according to the WHO 2021 classification - a retrospective analysis.","authors":"Enio Barci,Maximilian J Mair,Jonas Reis,Katharina Müller,Jera Isakaj,Ergi Istrefi,Isabelle von Polenz,Sophie C Siegmund,Lena Kaiser,Matthias Preusser,Christian Schichor,Niklas Thon,Patrick Harter,Louisa von Baumgarten,Robert Forbrig,Nathalie L Albert","doi":"10.1007/s00259-026-07760-2","DOIUrl":"https://doi.org/10.1007/s00259-026-07760-2","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"42 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1007/s00259-025-07695-0
Anna Pees,Ann-Kathrin Grotegerd,Daniel Bleher,Kristina Herfert,Neil Vasdev
The development of positron emission tomography (PET) tracers targeting α-synuclein (α-syn) aggregates remains a major challenge in PET imaging of neurodegenerative diseases. This review provides a comprehensive overview of the recent advances, key obstacles, and aims to give future directions for the development of α-syn PET tracers. The first part of the review focuses on the experimental strategies to develop potential α-syn PET ligands. We overview the differences between various types of α-syn fibrils, including preformed fibrils and patient-derived fibrils, and methods such as solid-state nuclear magnetic resonance and cryogenic electron microscopy used for structure elucidation of the fibrils. Furthermore, the review summarizes the techniques for the assessment of ligand binding to α-syn, such as fibril binding assays (competition and saturation binding assays), macro- and microautoradiography, and alternative methods like surface plasmon resonance and biolayer interferometry. Determination of pharmacokinetics and metabolism are likewise important steps in α-syn tracer development, and hurdles and merits of in vitro and in vivo methods are contemplated, in the context of translation to in vivo evaluation in fibril-inoculated and transgenic animal models. Finally, off-target binding of tracer candidates is described, which still remains one of the major pitfalls of α-syn-targeting PET tracers. The second part of the review overviews all small molecule α-syn PET tracers developed since 2022, highlighting their progress, current limitations, and future directions for achieving clinically viable α-syn PET imaging agents.
{"title":"PET imaging of alpha-synuclein: from radiotracer design through in vitro and in vivo translation.","authors":"Anna Pees,Ann-Kathrin Grotegerd,Daniel Bleher,Kristina Herfert,Neil Vasdev","doi":"10.1007/s00259-025-07695-0","DOIUrl":"https://doi.org/10.1007/s00259-025-07695-0","url":null,"abstract":"The development of positron emission tomography (PET) tracers targeting α-synuclein (α-syn) aggregates remains a major challenge in PET imaging of neurodegenerative diseases. This review provides a comprehensive overview of the recent advances, key obstacles, and aims to give future directions for the development of α-syn PET tracers. The first part of the review focuses on the experimental strategies to develop potential α-syn PET ligands. We overview the differences between various types of α-syn fibrils, including preformed fibrils and patient-derived fibrils, and methods such as solid-state nuclear magnetic resonance and cryogenic electron microscopy used for structure elucidation of the fibrils. Furthermore, the review summarizes the techniques for the assessment of ligand binding to α-syn, such as fibril binding assays (competition and saturation binding assays), macro- and microautoradiography, and alternative methods like surface plasmon resonance and biolayer interferometry. Determination of pharmacokinetics and metabolism are likewise important steps in α-syn tracer development, and hurdles and merits of in vitro and in vivo methods are contemplated, in the context of translation to in vivo evaluation in fibril-inoculated and transgenic animal models. Finally, off-target binding of tracer candidates is described, which still remains one of the major pitfalls of α-syn-targeting PET tracers. The second part of the review overviews all small molecule α-syn PET tracers developed since 2022, highlighting their progress, current limitations, and future directions for achieving clinically viable α-syn PET imaging agents.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"2 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: The study aimed to assess the impact of carbon-ion radiotherapy (CIRT) on intratumoral hypoxia in patients with locally advanced non-small cell lung cancer (LA-NSCLC) and the predictive value of 18F-fluoromisonidazole (FMISO) and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).
Methods: We retrospectively analyzed patients with stage IIB-IIIC NSCLC treated with CIRT who underwent baseline 18F-FMISO and 18F-FDG PET/CT and post-CIRT 18F-FMISO PET/CT. Regions of interest (ROIs) with a diameter ≥ 3 cm were analyzed. An ROI was defined as hypoxia with a tumor-to-muscle ratio (TMR) ≥ 1.4 on 18F-FMISO PET/CT. Survival outcomes were evaluated using Kaplan-Meier curves, and group comparisons were performed using Log-rank test.
Results: Thirty-seven eligible patients with 42 ROIs were included. Significant reductions in all 18F-FMISO parameters were observed after CIRT. ROIs with or without pre-CIRT hypoxia achieved similar local control (LC, with vs. without hypoxia: 75.5% vs. 85.5%, p = 0.799). The overlap ratios of hypoxic volumes between pre-/post-CIRT were 58.13%-81.34%. The combination of 18F-FDG uptake and post-CIRT hypoxia status demonstrated the strongest predictive value for LC (high vs. low uptake: 46.8% vs. 95.8%, p = 0.0004) with the highest area under the receiver operating characteristic curve (0.783, p = 0.01) among all evaluated combinations.
Conclusion: Tumor hypoxia detected by 18F-FMISO PET/CT was significantly decreased after CIRT in patients with LA-NSCLC. Similar LC was achieved in patients with or without pre-CIRT hypoxia, while post-CIRT hypoxia clearance resulted in a non-significant trend toward improved LC. Combining 18F-FMISO and 18F-FDG PET/CT might provide enhanced prognostic value. Further investigation is warranted to explore individualized CIRT dose painting strategies guided by multi-tracer PET/CT imaging.
目的：本研究旨在评估碳离子放疗（CIRT）对局部晚期非小细胞肺癌（LA-NSCLC）患者瘤内缺氧的影响以及18f -氟米唑（FMISO）和18f -氟脱氧葡萄糖（FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）的预测价值。方法：我们回顾性分析了接受CIRT治疗的IIB-IIIC期非小细胞肺癌患者，这些患者基线接受18F-FMISO和18F-FDG PET/CT检查，CIRT后接受18F-FMISO PET/CT检查。对直径≥3cm的感兴趣区域（roi）进行分析。ROI定义为缺氧，18F-FMISO PET/CT显示肿瘤与肌肉比(TMR)≥1.4。生存结果采用Kaplan-Meier曲线评价，组间比较采用Log-rank检验。结果：纳入37例符合条件的42例roi患者。CIRT后观察到所有18F-FMISO参数显著降低。有或没有cirt前缺氧的roi获得了相似的局部控制（LC，有和没有缺氧：75.5%对85.5%,p = 0.799）。cirt前后缺氧容积重叠率为58.13% ~ 81.34%。在所有评估的组合中，18F-FDG摄取和cirt后缺氧状态的组合对LC的预测价值最强（高摄取vs低摄取：46.8% vs 95.8%, p = 0.0004），受试者工作特征曲线下面积最大（0.783,p = 0.01）。结论：LA-NSCLC患者经CIRT后，18F-FMISO PET/CT检测到的肿瘤缺氧明显降低。在有或没有cirt前缺氧的患者中也实现了类似的LC，而cirt后缺氧清除导致LC改善的趋势不显著。结合18F-FMISO和18F-FDG PET/CT可能提供更高的预后价值。有必要进一步研究在多示踪PET/CT成像指导下的个体化CIRT剂量绘制策略。
{"title":"Impact of carbon-ion radiotherapy on tumor hypoxia detected by <sup>18</sup>F-FMISO PET/CT in locally advanced non-small cell lung cancer.","authors":"Jian Chen, Jingyi Cheng, Ningyi Ma, Jingfang Mao, Kai-Liang Wu, Guo-Liang Jiang","doi":"10.1007/s00259-025-07702-4","DOIUrl":"https://doi.org/10.1007/s00259-025-07702-4","url":null,"abstract":"<p><strong>Purpose: </strong>The study aimed to assess the impact of carbon-ion radiotherapy (CIRT) on intratumoral hypoxia in patients with locally advanced non-small cell lung cancer (LA-NSCLC) and the predictive value of <sup>18</sup>F-fluoromisonidazole (FMISO) and <sup>18</sup>F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).</p><p><strong>Methods: </strong>We retrospectively analyzed patients with stage IIB-IIIC NSCLC treated with CIRT who underwent baseline <sup>18</sup>F-FMISO and <sup>18</sup>F-FDG PET/CT and post-CIRT <sup>18</sup>F-FMISO PET/CT. Regions of interest (ROIs) with a diameter ≥ 3 cm were analyzed. An ROI was defined as hypoxia with a tumor-to-muscle ratio (TMR) ≥ 1.4 on <sup>18</sup>F-FMISO PET/CT. Survival outcomes were evaluated using Kaplan-Meier curves, and group comparisons were performed using Log-rank test.</p><p><strong>Results: </strong>Thirty-seven eligible patients with 42 ROIs were included. Significant reductions in all <sup>18</sup>F-FMISO parameters were observed after CIRT. ROIs with or without pre-CIRT hypoxia achieved similar local control (LC, with vs. without hypoxia: 75.5% vs. 85.5%, p = 0.799). The overlap ratios of hypoxic volumes between pre-/post-CIRT were 58.13%-81.34%. The combination of <sup>18</sup>F-FDG uptake and post-CIRT hypoxia status demonstrated the strongest predictive value for LC (high vs. low uptake: 46.8% vs. 95.8%, p = 0.0004) with the highest area under the receiver operating characteristic curve (0.783, p = 0.01) among all evaluated combinations.</p><p><strong>Conclusion: </strong>Tumor hypoxia detected by <sup>18</sup>F-FMISO PET/CT was significantly decreased after CIRT in patients with LA-NSCLC. Similar LC was achieved in patients with or without pre-CIRT hypoxia, while post-CIRT hypoxia clearance resulted in a non-significant trend toward improved LC. Combining <sup>18</sup>F-FMISO and <sup>18</sup>F-FDG PET/CT might provide enhanced prognostic value. Further investigation is warranted to explore individualized CIRT dose painting strategies guided by multi-tracer PET/CT imaging.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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