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}
OBJECTIVEBreast cancer is the most common malignancy among women and remains the leading cause of cancer-related death in this population. Radionuclide-based diagnostic and therapeutic approaches have emerged as effective and low-risk strategies for management of breast cancer. This study aimed to evaluate the diagnostic performance of [68Ga]Ga-FAP-2286 PET/CT compared with [18F]FDG PET/CT, and to provide a preliminary assessment of the clinical potential of [¹⁷⁷Lu]Lu-FAP-2286 radionuclide therapy in patients with advanced breast cancer.METHODSA total of twenty patients with clinically suspected recurrent or metastatic breast cancer were prospectively enrolled. All participants underwent both [18F]FDG PET/CT and [68Ga]Ga-FAP-2286 PET/CT imaging within one week. The positivity rate of lesions, maximum standardized uptake value (SUVmax), and tumor-to-background ratio (TBR) were compared between the two imaging modalities across different involved organs. In addition, four patients received a single cycle of [¹⁷⁷Lu]Lu-FAP-2286 radionuclide therapy, and were followed for 4 months to assess therapeutic response and safety.RESULTSThe total number of lesions detected by [68Ga]Ga-FAP-2286 PET/CT was significantly higher than that detected by [18F]FDG PET/CT (85.4% vs. 70.5%, P < 0.001). This superiority was particularly evident for hepatic metastases (94.7% vs. 68.9%, P < 0.001) and bone metastases (85.8% vs. 66.4%, P < 0.001). In contrast, both modalities demonstrated comparable sensitivity in identifying primary breast tumors (100% vs. 100%), regional lymph node metastases (85.4% vs. 81.4%, P = 0.388), and distant lymph node metastases (84.2% vs. 75.0%, P = 0.159). With respect to semiquantitative parameters, [68Ga]Ga-FAP-2286 PET/CT demonstrated significantly higher uptake in bone metastases than [18F]FDG PET/CT (SUVmax: 8.7 ± 3.9 vs. 6.7 ± 2.8, P = 0.002; TBR: 5.4 ± 2.2 vs. 3.8 ± 1.3, P < 0.001). However, for primary tumors, regional lymph nodes, distant lymph nodes, pulmonary metastases, and hepatic metastases, no statistically significant differences in SUVmax or TBR values were observed between the two tracers (all P > 0.05). [177Lu]Lu-FAP-2286 demonstrated sustained high tumor uptake up to 168 h post-injection. In the four treated patients, the mean absorbed doses to tumor lesions were 0.21 ± 0.09, 0.27 ± 0.14, 0.14 ± 0.05, and 1.02 ± 0.30 Gy/GBq, respectively. Notably, in one patient, the total absorbed dose for all tumor lesions reached 54.23 Gy/GBq at 168 h. No grade III or IV adverse events were observed, and three of four patients exhibited stable disease (SD) on follow-up.CONCLUSION[68Ga]Ga-FAP-2286 appears to be a promising imaging agent for breast cancer, while [177Lu]Lu-FAP-2286 may represent a potential therapeutic option for patients with advanced disease.
目的：乳腺癌是女性中最常见的恶性肿瘤，也是该人群中癌症相关死亡的主要原因。基于放射性核素的诊断和治疗方法已成为治疗乳腺癌的有效和低风险策略。本研究旨在评估[68Ga]Ga-FAP-2286 PET/CT与[18F]FDG PET/CT的诊断性能，并初步评估[¹⁷⁷Lu]Lu- fap -2286放射性核素治疗晚期乳腺癌患者的临床潜力。方法前瞻性纳入20例临床疑似复发或转移性乳腺癌患者。所有参与者在一周内同时进行[18F]FDG PET/CT和[68Ga]Ga-FAP-2286 PET/CT成像。比较不同受累器官的病变阳性率、最大标准化摄取值（SUVmax）和肿瘤与背景比（TBR）。此外，4名患者接受了单周期的[¹⁷⁷Lu]Lu- fap -2286放射性核素治疗，并随访4个月以评估治疗反应和安全性。结果[68Ga]Ga-FAP-2286 PET/CT检出病灶总数明显高于[18F]FDG PET/CT检出病灶总数（85.4% vs. 70.5%, P 0.05）。[177Lu]Lu-FAP-2286在注射后持续高肿瘤摄取至168 h。4例患者肿瘤病灶的平均吸收剂量分别为0.21±0.09、0.27±0.14、0.14±0.05和1.02±0.30 Gy/GBq。值得注意的是，有1例患者在168 h时，所有肿瘤病变的总吸收剂量达到54.23 Gy/GBq。未观察到III级或IV级不良事件，随访时4例患者中有3例病情稳定（SD）。结论[68Ga]Ga-FAP-2286似乎是一种很有前景的乳腺癌显像剂，而[177Lu]Lu-FAP-2286可能是晚期乳腺癌患者的潜在治疗选择。
{"title":"Comparative evaluation of [68Ga]Ga-FAP-2286 and [18F]FDG PET/CT in breast cancer and initial experience with [177Lu]Lu-FAP-2286 therapy.","authors":"Wei Liu,Na Zhang,Wenlu Zheng,Tingting Xu,Dong Huang,Zhiqiao Liu,Yue Chen","doi":"10.1007/s00259-026-07766-w","DOIUrl":"https://doi.org/10.1007/s00259-026-07766-w","url":null,"abstract":"OBJECTIVEBreast cancer is the most common malignancy among women and remains the leading cause of cancer-related death in this population. Radionuclide-based diagnostic and therapeutic approaches have emerged as effective and low-risk strategies for management of breast cancer. This study aimed to evaluate the diagnostic performance of [68Ga]Ga-FAP-2286 PET/CT compared with [18F]FDG PET/CT, and to provide a preliminary assessment of the clinical potential of [¹⁷⁷Lu]Lu-FAP-2286 radionuclide therapy in patients with advanced breast cancer.METHODSA total of twenty patients with clinically suspected recurrent or metastatic breast cancer were prospectively enrolled. All participants underwent both [18F]FDG PET/CT and [68Ga]Ga-FAP-2286 PET/CT imaging within one week. The positivity rate of lesions, maximum standardized uptake value (SUVmax), and tumor-to-background ratio (TBR) were compared between the two imaging modalities across different involved organs. In addition, four patients received a single cycle of [¹⁷⁷Lu]Lu-FAP-2286 radionuclide therapy, and were followed for 4 months to assess therapeutic response and safety.RESULTSThe total number of lesions detected by [68Ga]Ga-FAP-2286 PET/CT was significantly higher than that detected by [18F]FDG PET/CT (85.4% vs. 70.5%, P < 0.001). This superiority was particularly evident for hepatic metastases (94.7% vs. 68.9%, P < 0.001) and bone metastases (85.8% vs. 66.4%, P < 0.001). In contrast, both modalities demonstrated comparable sensitivity in identifying primary breast tumors (100% vs. 100%), regional lymph node metastases (85.4% vs. 81.4%, P = 0.388), and distant lymph node metastases (84.2% vs. 75.0%, P = 0.159). With respect to semiquantitative parameters, [68Ga]Ga-FAP-2286 PET/CT demonstrated significantly higher uptake in bone metastases than [18F]FDG PET/CT (SUVmax: 8.7 ± 3.9 vs. 6.7 ± 2.8, P = 0.002; TBR: 5.4 ± 2.2 vs. 3.8 ± 1.3, P < 0.001). However, for primary tumors, regional lymph nodes, distant lymph nodes, pulmonary metastases, and hepatic metastases, no statistically significant differences in SUVmax or TBR values were observed between the two tracers (all P > 0.05). [177Lu]Lu-FAP-2286 demonstrated sustained high tumor uptake up to 168 h post-injection. In the four treated patients, the mean absorbed doses to tumor lesions were 0.21 ± 0.09, 0.27 ± 0.14, 0.14 ± 0.05, and 1.02 ± 0.30 Gy/GBq, respectively. Notably, in one patient, the total absorbed dose for all tumor lesions reached 54.23 Gy/GBq at 168 h. No grade III or IV adverse events were observed, and three of four patients exhibited stable disease (SD) on follow-up.CONCLUSION[68Ga]Ga-FAP-2286 appears to be a promising imaging agent for breast cancer, while [177Lu]Lu-FAP-2286 may represent a potential therapeutic option for patients with advanced disease.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"48 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994836","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 : 2026-01-16DOI: 10.1007/s00259-025-07738-6
Rutger B. Henrar, Matthijs C. F. Cysouw, Xavier Palard-Novello, Lothar A. Schwarte, Pieter G. H. M. Raijmakers, Lioe-Fee de Geus-Oei, Alexander L. Vahrmeijer, Geert Kazemier, Albert D. Windhorst, Ronald Boellaard, Maqsood Yaqub, Daniela E. Oprea-Lager, Rutger-Jan Swijnenburg
Purpose Radiolabelled fibroblast activation protein inhibitors (FAPI) are promising molecular imaging tracers for the diagnosis and staging of pancreatobiliary cancer. To enable treatment response assessment with [ 68 Ga]Ga-FAPI-46, the day-to-day variability of its uptake must be defined. This study aimed to determine the repeatability of semi-quantitative [ 68 Ga]Ga-FAPI-46 PET/CT measurements in pancreatobiliary cancers. Methods Patients with pathologically confirmed pancreatobiliary cancer (pancreatic ductal adenocarcinoma (PDAC) or cholangiocarcinoma (CCA)) were included. Patients underwent two [ 68 Ga]Ga-FAPI-46 PET/CT scans, within 7 days, without any treatment before or between scans. Static long axial field-of-view (LAFOV) PET/CT scans were performed 60 min post-injection of [ 68 Ga]Ga-FAPI-46 (EARL2-compliant reconstruction). Suspected malignant lesions were semi-automatically delineated (local background-adjusted 50% isocontour of the peak standardised uptake value (SUV)) and semi-quantitative measurements were extracted (SUV mean , SUV peak and SUV max ). Tumour-to-background ratios (TBR) were also calculated. Repeatability was assessed using the repeatability coefficient (RC) and the intraclass correlation coefficient (ICC). Results Twelve patients were included (seven PDAC, three perihilar CCA and two intrahepatic CCA). The median injected dose was 216 MBq (interquartile range (IQR) 167–266 MBq) and the median uptake time was 60 min (range 60–68). In total, 70 FAPI-positive lesions were delineated. The RCs of SUV mean , SUV peak and SUV max were 23.7%, 23.9% and 29.8%, respectively. For the blood pool adjusted TBR mean , TBR peak and TBR max , the RC’s were 21.6%, 20.8% and 28.0%, respectively. All ICCs were above 0.98. Conclusion Semi-quantitative measurements of [ 68 Ga]Ga-FAPI-46 PET/CT have an excellent repeatability and can potentially be used in future studies to assess treatment response in pancreatobiliary cancers.
{"title":"Repeatability of semi-quantitative [68Ga]Ga-FAPI-46 PET/CT measurements in pancreatobiliary cancers: a test-retest study","authors":"Rutger B. Henrar, Matthijs C. F. Cysouw, Xavier Palard-Novello, Lothar A. Schwarte, Pieter G. H. M. Raijmakers, Lioe-Fee de Geus-Oei, Alexander L. Vahrmeijer, Geert Kazemier, Albert D. Windhorst, Ronald Boellaard, Maqsood Yaqub, Daniela E. Oprea-Lager, Rutger-Jan Swijnenburg","doi":"10.1007/s00259-025-07738-6","DOIUrl":"https://doi.org/10.1007/s00259-025-07738-6","url":null,"abstract":"Purpose Radiolabelled fibroblast activation protein inhibitors (FAPI) are promising molecular imaging tracers for the diagnosis and staging of pancreatobiliary cancer. To enable treatment response assessment with [ <jats:sup>68</jats:sup> Ga]Ga-FAPI-46, the day-to-day variability of its uptake must be defined. This study aimed to determine the repeatability of semi-quantitative [ <jats:sup>68</jats:sup> Ga]Ga-FAPI-46 PET/CT measurements in pancreatobiliary cancers. Methods Patients with pathologically confirmed pancreatobiliary cancer (pancreatic ductal adenocarcinoma (PDAC) or cholangiocarcinoma (CCA)) were included. Patients underwent two [ <jats:sup>68</jats:sup> Ga]Ga-FAPI-46 PET/CT scans, within 7 days, without any treatment before or between scans. Static long axial field-of-view (LAFOV) PET/CT scans were performed 60 min post-injection of [ <jats:sup>68</jats:sup> Ga]Ga-FAPI-46 (EARL2-compliant reconstruction). Suspected malignant lesions were semi-automatically delineated (local background-adjusted 50% isocontour of the peak standardised uptake value (SUV)) and semi-quantitative measurements were extracted (SUV <jats:sub>mean</jats:sub> , SUV <jats:sub>peak</jats:sub> and SUV <jats:sub>max</jats:sub> ). Tumour-to-background ratios (TBR) were also calculated. Repeatability was assessed using the repeatability coefficient (RC) and the intraclass correlation coefficient (ICC). Results Twelve patients were included (seven PDAC, three perihilar CCA and two intrahepatic CCA). The median injected dose was 216 MBq (interquartile range (IQR) 167–266 MBq) and the median uptake time was 60 min (range 60–68). In total, 70 FAPI-positive lesions were delineated. The RCs of SUV <jats:sub>mean</jats:sub> , SUV <jats:sub>peak</jats:sub> and SUV <jats:sub>max</jats:sub> were 23.7%, 23.9% and 29.8%, respectively. For the blood pool adjusted TBR <jats:sub>mean</jats:sub> , TBR <jats:sub>peak</jats:sub> and TBR <jats:sub>max</jats:sub> , the RC’s were 21.6%, 20.8% and 28.0%, respectively. All ICCs were above 0.98. Conclusion Semi-quantitative measurements of [ <jats:sup>68</jats:sup> Ga]Ga-FAPI-46 PET/CT have an excellent repeatability and can potentially be used in future studies to assess treatment response in pancreatobiliary cancers.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"5 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972531","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 : 2026-01-16DOI: 10.1007/s00259-025-07743-9
Greet Vanderlinden, Mathieu Vandenbulcke, Koen Van Laere
{"title":"High-resolution [18F]MK-6240 PET in Alzheimer’s disease","authors":"Greet Vanderlinden, Mathieu Vandenbulcke, Koen Van Laere","doi":"10.1007/s00259-025-07743-9","DOIUrl":"https://doi.org/10.1007/s00259-025-07743-9","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"60 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972022","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 : 2026-01-16DOI: 10.1007/s00259-025-07740-y
Vincent Bourbonne,P Lovinfosse,M Geier,R Le Pennec,R Abgral,K Pluchon,J N Choplain,B Duysinx,F Lallemand,Arnaud Uguen,R Hustinx,R Magwenzi,M Hatt,O Pradier,F Lucia
PURPOSE/OBJECTIVE(S)Accurate detection of occult lymph node metastasis (OLNM) in patients with localized non-small cell lung cancer (NSCLC) remains a clinical challenge. This study aimed to develop and validate a radiomics-based predictive model for OLNM.MATERIALS/METHODSA radiomics model (ModelPET) and a model (ModelCombined) combining radiomics and clinical features were developed using a retrospective monocentric cohort of localized NSCLC patients treated with surgery (Cohort A) and tested on an external cohort (Cohort B) of 112 localized NSCLC patients also treated with surgery (publicly available Radiogenomics cohort). The model was further assessed in an independent cohort of 488 patients with localized NSCLC who underwent definitive stereotactic body radiotherapy (SBRT) (Cohort C) using regional relapse free survival (RRFS) as a surrogate for OLNM. Radiomic features were extracted from pre-treatment FDG PET and combined to predict OLNM using a multilayer perceptron approach.RESULTSIn the training cohort, the ModelPET and ModelCombined achieved AUCs of 0.92/0.99 and balanced accuracies (Bacc) of 80.0%/85.3%, respectively. In the Cohort B, the ModelPET and ModelCombined resulted in AUCs of 0.73/0.67 and Baccs of 71.2%/51.7%, respectively. In the Cohort C, the predicted OLNM risk based on ModelPET was significantly associated with worse RFFS (HR 1.60 95% CI 1.03-2.48, p = 0.04). The ModelCombined was not associated with survival outcomes (p > 0.05).CONCLUSIONThis study presents a radiomics-based predictive model for OLNM in localized NSCLC, validated across several retrospective independent cohorts. Subject to a prospective evaluation, the model could be used to refine clinical decision-making.
目的/目的(S)准确检测局限性非小细胞肺癌（NSCLC）患者的隐匿性淋巴结转移（OLNM）仍然是一个临床挑战。本研究旨在开发和验证基于放射组学的OLNM预测模型。材料/方法：采用手术治疗的局部NSCLC患者的回顾性单中心队列（队列a）建立放射组学模型（ModelPET）和结合放射组学和临床特征的模型（ModelCombined），并在112例也接受手术治疗的局部NSCLC患者的外部队列（队列B）中进行测试（公开可用的放射基因组学队列）。该模型在488例局部NSCLC患者的独立队列中进一步进行了评估，这些患者接受了明确的立体定向放疗（SBRT）（队列C），使用区域无复发生存率（RRFS）作为OLNM的替代指标。从预处理的FDG PET中提取放射学特征，并使用多层感知器方法结合预测OLNM。结果在训练队列中，ModelPET和modelcombination的auc分别为0.92/0.99，平衡准确率（Bacc）分别为80.0%/85.3%。在队列B中，ModelPET和ModelCombined的auc分别为0.73/0.67，bacc分别为71.2%/51.7%。在队列C中，基于ModelPET预测的OLNM风险与较差的RFFS显著相关（HR 1.60 95% CI 1.03-2.48, p = 0.04）。ModelCombined与生存结果无相关性（p < 0.05）。本研究提出了一种基于放射组学的局部NSCLC OLNM预测模型，并在多个回顾性独立队列中得到验证。经过前瞻性评估，该模型可用于改进临床决策。
{"title":"Development and external validation of a FDG PET-based radiomics model predicting occult lymph node metastasis in non-small cell lung cancer patients.","authors":"Vincent Bourbonne,P Lovinfosse,M Geier,R Le Pennec,R Abgral,K Pluchon,J N Choplain,B Duysinx,F Lallemand,Arnaud Uguen,R Hustinx,R Magwenzi,M Hatt,O Pradier,F Lucia","doi":"10.1007/s00259-025-07740-y","DOIUrl":"https://doi.org/10.1007/s00259-025-07740-y","url":null,"abstract":"PURPOSE/OBJECTIVE(S)Accurate detection of occult lymph node metastasis (OLNM) in patients with localized non-small cell lung cancer (NSCLC) remains a clinical challenge. This study aimed to develop and validate a radiomics-based predictive model for OLNM.MATERIALS/METHODSA radiomics model (ModelPET) and a model (ModelCombined) combining radiomics and clinical features were developed using a retrospective monocentric cohort of localized NSCLC patients treated with surgery (Cohort A) and tested on an external cohort (Cohort B) of 112 localized NSCLC patients also treated with surgery (publicly available Radiogenomics cohort). The model was further assessed in an independent cohort of 488 patients with localized NSCLC who underwent definitive stereotactic body radiotherapy (SBRT) (Cohort C) using regional relapse free survival (RRFS) as a surrogate for OLNM. Radiomic features were extracted from pre-treatment FDG PET and combined to predict OLNM using a multilayer perceptron approach.RESULTSIn the training cohort, the ModelPET and ModelCombined achieved AUCs of 0.92/0.99 and balanced accuracies (Bacc) of 80.0%/85.3%, respectively. In the Cohort B, the ModelPET and ModelCombined resulted in AUCs of 0.73/0.67 and Baccs of 71.2%/51.7%, respectively. In the Cohort C, the predicted OLNM risk based on ModelPET was significantly associated with worse RFFS (HR 1.60 95% CI 1.03-2.48, p = 0.04). The ModelCombined was not associated with survival outcomes (p > 0.05).CONCLUSIONThis study presents a radiomics-based predictive model for OLNM in localized NSCLC, validated across several retrospective independent cohorts. Subject to a prospective evaluation, the model could be used to refine clinical decision-making.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"63 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986397","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}
PURPOSETo evaluate the prognostic value of baseline [68Ga]Ga-DOTA-NOC PET/CT-derived volumetric and uptake parameters in paediatric neuroblastoma patients.METHODSSixty‑five newly diagnosed patients underwent baseline [68Ga]Ga‑DOTA‑NOC PET/CT. Primary‑tumour and whole‑body metrics were measured: SUVmax, SUVmean, SUVpeak (standardized uptake values), Gross Tumour Volume (GTV), and Total Lesion NOC (TL‑NOC). Cox regression evaluated predictors of progression‑free survival (PFS) and overall survival (OS).RESULTSOver a median 30‑month follow‑up (range 10-51), 20 progressed and 11 died. High‑risk cases (n = 38) had higher uptake and volumes than non high‑risk (n = 27): primary‑tumour and whole‑body SUVmax (p = 0.006 and 0.001); primary‑tumour SUVpeak (p = 0.013); whole‑body TL‑NOC(p = 0.001) and GTV (p = 0.016). On multivariable Cox analysis, primary‑tumour SUVmax (HR = 1.07, 95% CI: 1.02-1.12, P = 0.005) and SUVpeak (HR = 1.06, 95% CI: 1.01-1.11, P = 0.025), as well as whole‑body TL‑NOC (per 100 SUV × cm3; HR = 1.03, 95% CI: 1.01-1.05, P = 0.013), remained independently associated with PFS, whereas whole‑body TL‑NOC (per 100 SUV × cm3; HR = 1.07, 95% CI: 1.03-1.10, P = 0.001), whole‑body GTV (per 50 cm3; HR = 1.08, 95% CI: 1.01-1.16, P = 0.028) and primary‑tumour TL‑NOC (per 100 SUV × cm3; HR = 1.08, 95% CI: 1.01-1.15, P = 0.026) were independent predictors of OS. A whole‑body TL‑NOC > 1357.05 SUV × cm3 identified patients with significantly worse PFS and OS.CONCLUSIONParameters derived from [68Ga]Ga‑DOTA‑NOC PET/CT, especially whole‑body TL‑NOC, are independent predictors of PFS and OS in neuroblastoma, supporting their use for risk stratification.
{"title":"Prognostic value of baseline [68Ga]Ga‑DOTA‑NOC PET/CT in paediatric neuroblastoma.","authors":"Qinfeng Xu,Yueran Chen,Jieping Song,Wanhua Guo,Guoqiang Shao","doi":"10.1007/s00259-025-07745-7","DOIUrl":"https://doi.org/10.1007/s00259-025-07745-7","url":null,"abstract":"PURPOSETo evaluate the prognostic value of baseline [68Ga]Ga-DOTA-NOC PET/CT-derived volumetric and uptake parameters in paediatric neuroblastoma patients.METHODSSixty‑five newly diagnosed patients underwent baseline [68Ga]Ga‑DOTA‑NOC PET/CT. Primary‑tumour and whole‑body metrics were measured: SUVmax, SUVmean, SUVpeak (standardized uptake values), Gross Tumour Volume (GTV), and Total Lesion NOC (TL‑NOC). Cox regression evaluated predictors of progression‑free survival (PFS) and overall survival (OS).RESULTSOver a median 30‑month follow‑up (range 10-51), 20 progressed and 11 died. High‑risk cases (n = 38) had higher uptake and volumes than non high‑risk (n = 27): primary‑tumour and whole‑body SUVmax (p = 0.006 and 0.001); primary‑tumour SUVpeak (p = 0.013); whole‑body TL‑NOC(p = 0.001) and GTV (p = 0.016). On multivariable Cox analysis, primary‑tumour SUVmax (HR = 1.07, 95% CI: 1.02-1.12, P = 0.005) and SUVpeak (HR = 1.06, 95% CI: 1.01-1.11, P = 0.025), as well as whole‑body TL‑NOC (per 100 SUV × cm3; HR = 1.03, 95% CI: 1.01-1.05, P = 0.013), remained independently associated with PFS, whereas whole‑body TL‑NOC (per 100 SUV × cm3; HR = 1.07, 95% CI: 1.03-1.10, P = 0.001), whole‑body GTV (per 50 cm3; HR = 1.08, 95% CI: 1.01-1.16, P = 0.028) and primary‑tumour TL‑NOC (per 100 SUV × cm3; HR = 1.08, 95% CI: 1.01-1.15, P = 0.026) were independent predictors of OS. A whole‑body TL‑NOC > 1357.05 SUV × cm3 identified patients with significantly worse PFS and OS.CONCLUSIONParameters derived from [68Ga]Ga‑DOTA‑NOC PET/CT, especially whole‑body TL‑NOC, are independent predictors of PFS and OS in neuroblastoma, supporting their use for risk stratification.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"39 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986395","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 : 2026-01-14DOI: 10.1007/s00259-025-07744-8
Gabriel T Sheikh,Sophie C Siegmund,Liam Widjaja,Sarah L Takayama Fouladgar,Astrid Delker,Jozefina Casuscelli,Lena M Unterrainer,Rudolf A Werner,Mathias J Zacherl
PURPOSE225Ac-Targeted alpha therapy is a potent and promising option for patients with metastatic castration-resistant prostate cancer (mCRPC) and failure of guideline-based therapies and 177Lu-PSMA-radioligand therapy. Unfortunately, side effects associated with TAT can significantly affect quality of life. A combination treatment regimen adding 177Lu and reducing 225Ac activities may mitigate side effects while preserving sufficient anti-tumour efficacy. We therefore evaluated different combinations [225Ac]Ac-/[177Lu]Lu-PSMA-I&T (ALCT) with regard to response and adverse events.METHODSA total of 19 consecutive patients treated with ALCT on compassionate use basis at our department were evaluated. Patients were divided into two different subgroups, depending on the 225Ac/177Lu-activity administered: group 1 (Gr1) received 4MBq and 4000MBq, group 2 (Gr2) 8 MBq and 1000MBq per therapy cycle, respectively. Laboratory (PSA, ALP, LDH, Hb, Lc, Tc, Crea) and imaging parameters on [18F]PSMA-1007-PET/CTs (TTV, SUVmax/mean) at baseline and after 2 cycles of therapy were evaluated for the total patient population as well as each therapy subgroup and statistically compared. Adverse events (xerostomia, anemia, leukopenia, thrombocytopenia, weight loss) were recorded. Response evaluation criteria in PSMA-PET/CT (RECIP 1.0) was used for response evaluation.RESULTSAccording to the RECIP composite classification, 4 of 10 (40%) of patients from Gr1 and 5 of 9 (56%) from Gr2 showed a partial response, while 4/10 (40%) and 2/9 (22%) of patients from Gr1 and 2, respectively, showed progressive disease. After 2 cycles of ALCT the following adverse events newly developed or worsened by at least one grade: anemia in 2/10 (20%) patients from Gr1 and 3/9 (33%) patients from Gr2; thrombocytopenia in 1/10 (10%) patients from Gr1; leukopenia in 4/10 (40%) from Gr1 and 2/9 (22%) from Gr2; weight loss in 1/10 (10%) from Gr1 and 2/9 (22%) from Gr2 and xerostomia in 3/10 (30%) from Gr1 and 5/9 (56%) from Gr2. There was no significant difference between the two groups in respect to absolute values after therapy or pre- and post-therapy difference in any of the laboratory or imaging parameters evaluated.CONCLUSIONAlthough no significant difference in response or adverse events could be found between the two treatment groups, ALCT with higher 225Ac-activities seems to favor a better outcome, albeit at the cost of a higher risk of xerostomia. ALCT with lower 225Ac activities may be a good choice when conserving salivary gland function and therefore quality of life is of higher concern, but renders more careful monitoring of blood values necessary.
{"title":"Systematic evaluation of response and adverse events in mCRPC patients treated with different combinations of [225Ac]Ac/[177Lu]Lu-PSMA-therapy.","authors":"Gabriel T Sheikh,Sophie C Siegmund,Liam Widjaja,Sarah L Takayama Fouladgar,Astrid Delker,Jozefina Casuscelli,Lena M Unterrainer,Rudolf A Werner,Mathias J Zacherl","doi":"10.1007/s00259-025-07744-8","DOIUrl":"https://doi.org/10.1007/s00259-025-07744-8","url":null,"abstract":"PURPOSE225Ac-Targeted alpha therapy is a potent and promising option for patients with metastatic castration-resistant prostate cancer (mCRPC) and failure of guideline-based therapies and 177Lu-PSMA-radioligand therapy. Unfortunately, side effects associated with TAT can significantly affect quality of life. A combination treatment regimen adding 177Lu and reducing 225Ac activities may mitigate side effects while preserving sufficient anti-tumour efficacy. We therefore evaluated different combinations [225Ac]Ac-/[177Lu]Lu-PSMA-I&T (ALCT) with regard to response and adverse events.METHODSA total of 19 consecutive patients treated with ALCT on compassionate use basis at our department were evaluated. Patients were divided into two different subgroups, depending on the 225Ac/177Lu-activity administered: group 1 (Gr1) received 4MBq and 4000MBq, group 2 (Gr2) 8 MBq and 1000MBq per therapy cycle, respectively. Laboratory (PSA, ALP, LDH, Hb, Lc, Tc, Crea) and imaging parameters on [18F]PSMA-1007-PET/CTs (TTV, SUVmax/mean) at baseline and after 2 cycles of therapy were evaluated for the total patient population as well as each therapy subgroup and statistically compared. Adverse events (xerostomia, anemia, leukopenia, thrombocytopenia, weight loss) were recorded. Response evaluation criteria in PSMA-PET/CT (RECIP 1.0) was used for response evaluation.RESULTSAccording to the RECIP composite classification, 4 of 10 (40%) of patients from Gr1 and 5 of 9 (56%) from Gr2 showed a partial response, while 4/10 (40%) and 2/9 (22%) of patients from Gr1 and 2, respectively, showed progressive disease. After 2 cycles of ALCT the following adverse events newly developed or worsened by at least one grade: anemia in 2/10 (20%) patients from Gr1 and 3/9 (33%) patients from Gr2; thrombocytopenia in 1/10 (10%) patients from Gr1; leukopenia in 4/10 (40%) from Gr1 and 2/9 (22%) from Gr2; weight loss in 1/10 (10%) from Gr1 and 2/9 (22%) from Gr2 and xerostomia in 3/10 (30%) from Gr1 and 5/9 (56%) from Gr2. There was no significant difference between the two groups in respect to absolute values after therapy or pre- and post-therapy difference in any of the laboratory or imaging parameters evaluated.CONCLUSIONAlthough no significant difference in response or adverse events could be found between the two treatment groups, ALCT with higher 225Ac-activities seems to favor a better outcome, albeit at the cost of a higher risk of xerostomia. ALCT with lower 225Ac activities may be a good choice when conserving salivary gland function and therefore quality of life is of higher concern, but renders more careful monitoring of blood values necessary.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"52 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961411","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}
PURPOSEWe previously proposed that a probability-based sympathetic 123I-meta-iodobenzylguanidine (mIBG) index (SMILe) could distinguish the presence or absence of Lewy body disease (LBD) based on findings at a single center. However, whether the model would be useful in the real world remained uncertain. Therefore, we updated and evaluated its performance at five Japanese and three European institutions.METHODSWe compared data from 967 patients with suspected LBD with 62 controls from a normal database (NDB). Of 815 patients with guideline-based diagnoses, 483 had LBD (Parkinson disease [PD] or dementia with Lewy bodies [DLB]) and 332 did not have LBD. Heart-to-mediastinum (H/M) ratios were standardized using a phantom-based method. Logistic regression models included early and late H/M ratios, age, sex, and comorbidities. We assessed diagnostic performance using ROC analysis and cross-validation.RESULTSThe updated model discriminated LBD from other diseases (AUC for early and late H/M, 0.880 0.899, respectively). Age correction of H/M ratios based on the NDB did not improve accuracy. Median early H/M ratios [SMILe probability] were 3.09 [12.8%] for NDB, 2.57 [37.5%] for Alzheimer disease, 1.76 [84.7%] for PD, and 1.62 [89.0%] for DLB, with significantly lower H/M ratios and higher probabilities in PD and DLB compared with controls (p < 0.0001). Late-phase imaging added value mainly in intermediate borderline (30%-70%) situations. Coronary artery disease attenuated the diagnostic performance of SMILe.CONCLUSIONThe probability-based 123I-mIBG model reliably differentiated LBD from other diseases. Standardization among sites supports global applicability and reflects real-world clinical practice.
{"title":"Multicenter development and validation of a probability-based model to diagnose Lewy body disease using ¹²³I-meta-iodobenzylguanidine.","authors":"Kenichi Nakajima,Junji Komatsu,Takeshi Matsumura,Satoshi Orimo,Mitsuhiro Yoshita,Viviana Frantellizzi,Maria Silvia De Feo,Gemma Greenfinch,Alan Thomas,Roberta Assante,Wanda Acampa,Naoki Shirasaki,Kunihiko Yokoyama,Hiroshi Wakabayashi,Moeko Noguchi-Shinohara,Kenjiro Ono,Seigo Kinuya","doi":"10.1007/s00259-025-07706-0","DOIUrl":"https://doi.org/10.1007/s00259-025-07706-0","url":null,"abstract":"PURPOSEWe previously proposed that a probability-based sympathetic 123I-meta-iodobenzylguanidine (mIBG) index (SMILe) could distinguish the presence or absence of Lewy body disease (LBD) based on findings at a single center. However, whether the model would be useful in the real world remained uncertain. Therefore, we updated and evaluated its performance at five Japanese and three European institutions.METHODSWe compared data from 967 patients with suspected LBD with 62 controls from a normal database (NDB). Of 815 patients with guideline-based diagnoses, 483 had LBD (Parkinson disease [PD] or dementia with Lewy bodies [DLB]) and 332 did not have LBD. Heart-to-mediastinum (H/M) ratios were standardized using a phantom-based method. Logistic regression models included early and late H/M ratios, age, sex, and comorbidities. We assessed diagnostic performance using ROC analysis and cross-validation.RESULTSThe updated model discriminated LBD from other diseases (AUC for early and late H/M, 0.880 0.899, respectively). Age correction of H/M ratios based on the NDB did not improve accuracy. Median early H/M ratios [SMILe probability] were 3.09 [12.8%] for NDB, 2.57 [37.5%] for Alzheimer disease, 1.76 [84.7%] for PD, and 1.62 [89.0%] for DLB, with significantly lower H/M ratios and higher probabilities in PD and DLB compared with controls (p < 0.0001). Late-phase imaging added value mainly in intermediate borderline (30%-70%) situations. Coronary artery disease attenuated the diagnostic performance of SMILe.CONCLUSIONThe probability-based 123I-mIBG model reliably differentiated LBD from other diseases. Standardization among sites supports global applicability and reflects real-world clinical practice.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"10 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961408","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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