Pub Date : 2026-02-01Epub Date: 2025-08-25DOI: 10.1007/s00259-025-07519-1
Marcel Schwinger, Charis Kalogirou, Vincent Scheper, Maximiliane Däuwel, Simon Weber, Anna Katharina Seitz, Hubert Kübler, Andreas K Buck, Rudolf A Werner, Philipp E Hartrampf
Purpose: We aimed to evaluate the safety and efficacy to explore predictors of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA I&T in metastatic castration-resistant prostate cancer (mCRPC) patients aged ≥ 75 and explored baseline predictors of overall survival (OS).
Materials and methods: 56 men (median age 78, range 75-95) were treated with RLT. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Baseline Gleason score, blood parameters (PSA, LDH), and sites of metastases (bone, lymph nodes, liver, lung) were recorded. Quantitative PET parameters such as SUVmean (mean standardized uptake value), SUVpeak (peak standardized uptake value), SUVmax (maximum standardized uptake value), PSMA-TV (PSMApositive tumor volume), TL-PSMA (total lesion PSMA) were measured. PET response was assessed by RECIP 1.0 (response evaluation criteria in PSMA imaging); biochemical response by PCWG3 (prostate cancer working group 3). Associations with OS were analyzed via uni- and multivariable Cox regression and Kaplan-Meier curves.
Results: No CTCAE grade III-V toxicities occurred. Grade I/II hematologic events included anemia (23.2%), leukocytopenia (18.6%) and thrombocytopenia (9.3%); eGFR declined by 2.5% (grade I/II in 18.6%). Median OS was 11 months; 60.7% of patients died. 74.4% of patients (32/43) showed PSA declines (median - 58%; 14/43 ≥ 50%). Higher baseline PSA (HR 1.001 per ng/mL; P < 0.10) and LDH (HR 1.008 per U/L; P < 0.01) were associated with shorter OS. Patients with progressive disease by both RECIP and PCWG3 had shorter OS than others (11 vs. 22 months; HR 3.3; P < 0.01). Any PSA response predicted longer OS (21 vs. 7 months; HR 0.3; P < 0.01). Presence of liver metastases portended poorer survival (8 vs. 21 months; HR 6.7; P < 0.001).
Conclusion: [¹⁷⁷Lu]Lu-PSMA I&T RLT is well tolerated in patients ≥ 75 years. Lower baseline PSA and LDH but not PSMA-TV predict longer OS. Early PSA response strongly correlates with improved survival. Combined use of RECIP and PCWG3 criteria optimizes response assessment.
{"title":"Radioligand treatment with [<sup>177</sup>Lu]Lu-PSMA I&T in elderly Patients - Safety, efficacy, and prognostic factors for survival.","authors":"Marcel Schwinger, Charis Kalogirou, Vincent Scheper, Maximiliane Däuwel, Simon Weber, Anna Katharina Seitz, Hubert Kübler, Andreas K Buck, Rudolf A Werner, Philipp E Hartrampf","doi":"10.1007/s00259-025-07519-1","DOIUrl":"10.1007/s00259-025-07519-1","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to evaluate the safety and efficacy to explore predictors of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA I&T in metastatic castration-resistant prostate cancer (mCRPC) patients aged ≥ 75 and explored baseline predictors of overall survival (OS).</p><p><strong>Materials and methods: </strong>56 men (median age 78, range 75-95) were treated with RLT. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Baseline Gleason score, blood parameters (PSA, LDH), and sites of metastases (bone, lymph nodes, liver, lung) were recorded. Quantitative PET parameters such as SUVmean (mean standardized uptake value), SUVpeak (peak standardized uptake value), SUVmax (maximum standardized uptake value), PSMA-TV (PSMApositive tumor volume), TL-PSMA (total lesion PSMA) were measured. PET response was assessed by RECIP 1.0 (response evaluation criteria in PSMA imaging); biochemical response by PCWG3 (prostate cancer working group 3). Associations with OS were analyzed via uni- and multivariable Cox regression and Kaplan-Meier curves.</p><p><strong>Results: </strong>No CTCAE grade III-V toxicities occurred. Grade I/II hematologic events included anemia (23.2%), leukocytopenia (18.6%) and thrombocytopenia (9.3%); eGFR declined by 2.5% (grade I/II in 18.6%). Median OS was 11 months; 60.7% of patients died. 74.4% of patients (32/43) showed PSA declines (median - 58%; 14/43 ≥ 50%). Higher baseline PSA (HR 1.001 per ng/mL; P < 0.10) and LDH (HR 1.008 per U/L; P < 0.01) were associated with shorter OS. Patients with progressive disease by both RECIP and PCWG3 had shorter OS than others (11 vs. 22 months; HR 3.3; P < 0.01). Any PSA response predicted longer OS (21 vs. 7 months; HR 0.3; P < 0.01). Presence of liver metastases portended poorer survival (8 vs. 21 months; HR 6.7; P < 0.001).</p><p><strong>Conclusion: </strong>[¹⁷⁷Lu]Lu-PSMA I&T RLT is well tolerated in patients ≥ 75 years. Lower baseline PSA and LDH but not PSMA-TV predict longer OS. Early PSA response strongly correlates with improved survival. Combined use of RECIP and PCWG3 criteria optimizes response assessment.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"1469-1478"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947351","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 : 2026-02-01Epub Date: 2025-06-06DOI: 10.1007/s00259-025-07387-9
Hongyan Yin, Hongcheng Shi
{"title":"<sup>18</sup>F-FDG PET/CT in pectoralis major myositis.","authors":"Hongyan Yin, Hongcheng Shi","doi":"10.1007/s00259-025-07387-9","DOIUrl":"10.1007/s00259-025-07387-9","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"1363-1364"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233583","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 : 2026-02-01Epub Date: 2025-08-23DOI: 10.1007/s00259-025-07512-8
Liang Zhao, Yizhen Pang, Daqiang Xu, Jianhao Chen, Shan Yu, Dan Ruan, Lingyu Yu, Zhenyu Wu, Guoqiang Su, Hua Wu, Lin Ai, Long Sun, Di Fan, Haojun Chen
Purpose: Accurate delineation of tumor margins and maximal safe resection are critical for successful curative oncologic surgery. However, fibroblast activation protein (FAP)-targeted probes suitable for fluorescence imaging remain limited. Here, we developed novel FAP-targeted fluorescent probes to accurately delineate tumor margins and enable rapid intraoperative identification of tumor boundaries in resected specimens.
Methods: DOTA chelator for radiolabelling with gallium-68 was incorporated into dual-modality FAP-targeted probes synthesised by conjugating FAP-2286 and 3BP-3940 with the near-infrared (NIR) fluorophore IRDye800CW. These probes were evaluated both in vitro and in vivo using HEK293T-FAP cells stably expressing FAP and xenograft mouse models. Positron emission tomography (PET) and (NIR-II) fluorescence imaging assessed the specificity and ability of probes to delineate tumor margins. For clinical validation, resected lung tissue was incubated ex vivo with the probes. Tumor regions and margins were identified using fluorescence imaging and subsequently validated by haematoxylin and eosin (H&E) staining and FAP immunohistochemistry.
Results: Both IRDye800CW-FAP-2286 and IRDye800CW-3BP-3940 exhibited high affinity for FAP-positive cells in vitro. PET imaging revealed high tumor specificity for both probes in vivo. In vivo and ex vivo NIR-II fluorescence imaging enabled accurate visualisation of tumor margins, with IRDye800CW-3BP-3940 exhibiting superior performance compared with IRDye800CW-FAP-2286. In the clinical specimen, IRDye800CW-3BP-3940 successfully delineated tumor regions with strong concordance to histopathological findings.
Conclusion: We developed and validated a novel dual-modality molecular probe, IRDye800CW-3BP-3940, which integrated PET and NIR fluorescence imaging capabilities. This probe enabled highly specific detection of FAP-positive tumors and precise delineation of tumor margins in resected specimens.
{"title":"Preclinical and pilot clinical evaluation of novel dual-modality pet/fluorescence probes targeting FAP for accurate tumor margin delineation.","authors":"Liang Zhao, Yizhen Pang, Daqiang Xu, Jianhao Chen, Shan Yu, Dan Ruan, Lingyu Yu, Zhenyu Wu, Guoqiang Su, Hua Wu, Lin Ai, Long Sun, Di Fan, Haojun Chen","doi":"10.1007/s00259-025-07512-8","DOIUrl":"10.1007/s00259-025-07512-8","url":null,"abstract":"<p><strong>Purpose: </strong>Accurate delineation of tumor margins and maximal safe resection are critical for successful curative oncologic surgery. However, fibroblast activation protein (FAP)-targeted probes suitable for fluorescence imaging remain limited. Here, we developed novel FAP-targeted fluorescent probes to accurately delineate tumor margins and enable rapid intraoperative identification of tumor boundaries in resected specimens.</p><p><strong>Methods: </strong>DOTA chelator for radiolabelling with gallium-68 was incorporated into dual-modality FAP-targeted probes synthesised by conjugating FAP-2286 and 3BP-3940 with the near-infrared (NIR) fluorophore IRDye800CW. These probes were evaluated both in vitro and in vivo using HEK293T-FAP cells stably expressing FAP and xenograft mouse models. Positron emission tomography (PET) and (NIR-II) fluorescence imaging assessed the specificity and ability of probes to delineate tumor margins. For clinical validation, resected lung tissue was incubated ex vivo with the probes. Tumor regions and margins were identified using fluorescence imaging and subsequently validated by haematoxylin and eosin (H&E) staining and FAP immunohistochemistry.</p><p><strong>Results: </strong>Both IRDye800CW-FAP-2286 and IRDye800CW-3BP-3940 exhibited high affinity for FAP-positive cells in vitro. PET imaging revealed high tumor specificity for both probes in vivo. In vivo and ex vivo NIR-II fluorescence imaging enabled accurate visualisation of tumor margins, with IRDye800CW-3BP-3940 exhibiting superior performance compared with IRDye800CW-FAP-2286. In the clinical specimen, IRDye800CW-3BP-3940 successfully delineated tumor regions with strong concordance to histopathological findings.</p><p><strong>Conclusion: </strong>We developed and validated a novel dual-modality molecular probe, IRDye800CW-3BP-3940, which integrated PET and NIR fluorescence imaging capabilities. This probe enabled highly specific detection of FAP-positive tumors and precise delineation of tumor margins in resected specimens.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"1479-1490"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947360","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 : 2026-02-01Epub Date: 2025-08-28DOI: 10.1007/s00259-025-07520-8
Johannes Lohmeier, Jenny Meinhardt, Helena Radbruch, Mauricio Reyes, Winfried Brenner, Anna Tietze, Marcus R Makowski
Purpose: The isocitrate dehydrogenase (IDH) genotype is crucial for diagnosing and managing adult-type diffuse glioma. We investigated spatial tumour characteristics in treatment-naïve glioma using an U-Net-based CNN and evaluated associations with metabolic dysfunction and IDH genotype.
Methods: Between 2015 and 2024 patients with confirmed contrast-enhancing glioma were pre-operatively investigated using MRI or [18 F]FET PET/MRI. Automated morphometry using a U-Net-based CNN on standard MRI sequences (T1c, T1, T2, FLAIR) was performed. Contrast-enhancing tumour fraction (CTF), metabolic tumour volume (MTV), total tumour volume (TTV) were determined. Dice coefficient assessed volume intersections. Comparative and statistical analyses included non-parametric tests, ROC curves, regression, and correlation.
Results: A total of 180 patients (male, 114; female, 66; age, M ± SD = 54 ± 15y; IDH-mutant, 63; IDH wild-type, 117) with treatment-naïve glioma were evaluated. [18 F]FET-PET metabolic activity correlated significantly with CTF (p < .05). IDH-mutant gliomas had lower CTF (p < .001) due to higher non-enhancing tumour mass (p < .001) relative to the enhancing mass, unlike IDH wild-type glioblastoma. The CTF predicted IDH genotype with high accuracy (AUC = 0.85, sensitivity 78%, specificity 90%) across datasets. Combining CTF with patient age or SUVmax further improved the classification (ΔAUC = 0.12, p = .02; ΔAUC = 0.09, p > .05). Subgroup analyses showed consistent performance across IDH-mutant subtypes. MTV from [18 F]FET-PET exceeded structurally apparent TTV (p = .033).
Conclusion: Spatial mapping of treatment-naïve glioma identified a non-invasive biomarker, which is linked to metabolic dysfunction and enabled robust IDH-genotype classification from standard MRI, suggesting a central role for radiogenomic assessment in adult-type diffuse gliomas prior to surgery.
{"title":"Spatial tumour characteristics as an indirect marker of metabolic dysregulation: evaluation for non-invasive IDH-genotyping of glioma using hybrid [18 F]FET-PET/MRI.","authors":"Johannes Lohmeier, Jenny Meinhardt, Helena Radbruch, Mauricio Reyes, Winfried Brenner, Anna Tietze, Marcus R Makowski","doi":"10.1007/s00259-025-07520-8","DOIUrl":"10.1007/s00259-025-07520-8","url":null,"abstract":"<p><strong>Purpose: </strong>The isocitrate dehydrogenase (IDH) genotype is crucial for diagnosing and managing adult-type diffuse glioma. We investigated spatial tumour characteristics in treatment-naïve glioma using an U-Net-based CNN and evaluated associations with metabolic dysfunction and IDH genotype.</p><p><strong>Methods: </strong>Between 2015 and 2024 patients with confirmed contrast-enhancing glioma were pre-operatively investigated using MRI or [18 F]FET PET/MRI. Automated morphometry using a U-Net-based CNN on standard MRI sequences (T1c, T1, T2, FLAIR) was performed. Contrast-enhancing tumour fraction (CTF), metabolic tumour volume (MTV), total tumour volume (TTV) were determined. Dice coefficient assessed volume intersections. Comparative and statistical analyses included non-parametric tests, ROC curves, regression, and correlation.</p><p><strong>Results: </strong>A total of 180 patients (male, 114; female, 66; age, M ± SD = 54 ± 15y; IDH-mutant, 63; IDH wild-type, 117) with treatment-naïve glioma were evaluated. [18 F]FET-PET metabolic activity correlated significantly with CTF (p < .05). IDH-mutant gliomas had lower CTF (p < .001) due to higher non-enhancing tumour mass (p < .001) relative to the enhancing mass, unlike IDH wild-type glioblastoma. The CTF predicted IDH genotype with high accuracy (AUC = 0.85, sensitivity 78%, specificity 90%) across datasets. Combining CTF with patient age or SUVmax further improved the classification (ΔAUC = 0.12, p = .02; ΔAUC = 0.09, p > .05). Subgroup analyses showed consistent performance across IDH-mutant subtypes. MTV from [18 F]FET-PET exceeded structurally apparent TTV (p = .033).</p><p><strong>Conclusion: </strong>Spatial mapping of treatment-naïve glioma identified a non-invasive biomarker, which is linked to metabolic dysfunction and enabled robust IDH-genotype classification from standard MRI, suggesting a central role for radiogenomic assessment in adult-type diffuse gliomas prior to surgery.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"1939-1950"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-08-30DOI: 10.1007/s00259-025-07521-7
Silvia Carraro, Valentina A Ferraro, Pietro Zucchetta, Stefania Zanconato, Francesca Serani, Chiara Giraudo, Diego Cecchin
Background: Primary ciliary dyskinesia (PCD) is a rare condition characterized by ciliary dysfunction, impaired mucociliary clearance and mucus accumulation in the airways.
Purpose: Our aim was to evaluate the performance of [18F]FDG PET/MR in assessing structural and inflammatory pulmonary features in patients with PCD, using high-resolution CT (HRCT) as the gold-standard reference.
Materials and methods: We recruited patients with PCD (≥ 7 years) regularly followed at our Regional Center for PCD. They underwent chest HRCT and [18F]FDG PET/MR using sequences optimized for the morpho-functional study of the lung. Parametric PET images were obtained by dividing each voxel by the mean value in a reference area. The volume of interest (VOI in cm3), named Metabolic Inflammatory Volume (MIV), was calculated by thresholding the PET parametric image using a value twice the mean of the reference area. Standardized Uptake Value (SUV) Max, SUV mean, Total Lesion Glycolysis (TLG) and MIV were recorded. HRCT and MR were analyzed using the Eichinger score.
Results: Sixteen patients were enrolled. The Bland-Altman plot showed good agreement between HRCT and MR scores. Cumulative HRCT and MR scores correlated significantly with SUV mean score (HRCT: p = 0.02, rs=0.6; MR: p = 0.006, rs=0.66) and MIV (HRCT: p = 0.003, rs =0.7; MR: p = 0.004, rs =0.69). Total HRCT and MR scores and MIV score inversely correlated with spirometric parameters.
Conclusion: PET/MR proved to be accurate in evaluating disease extent in PCD. It enabled the simultaneous assessment of structural damage and lung inflammation, both of which resulted inversely related to lung function. PET/MR is a promising tool for PCD monitoring.
背景：原发性纤毛运动障碍（PCD）是一种罕见的疾病，其特征是纤毛功能障碍，纤毛粘膜清除受损和气道粘液积聚。目的：我们的目的是评估[18F]FDG PET/MR在评估PCD患者肺部结构和炎症性特征方面的表现，以高分辨率CT （HRCT）作为金标准参考。材料和方法：我们招募了PCD患者（≥7年），在我们的PCD区域中心定期随访。他们接受了胸部HRCT和[18F]FDG PET/MR，使用优化的肺部形态功能研究序列。参数化PET图像由每个体素除以参考区域的平均值得到。感兴趣的体积（VOI，以cm3为单位），称为代谢炎症体积（MIV），通过使用参考区域平均值的两倍的值对PET参数图像进行阈值计算。记录标准化摄取值（SUV） Max、SUV均值、病灶糖酵解总量（TLG）和MIV。采用Eichinger评分对HRCT和MR进行分析。结果：16例患者入组。Bland-Altman图显示HRCT和MR评分吻合良好。累积HRCT和MR评分与SUV平均评分（HRCT: p = 0.02, rs=0.6; MR: p = 0.006, rs=0.66）和MIV （HRCT: p = 0.003, rs= 0.7; MR: p = 0.004, rs= 0.69）显著相关。HRCT和MR总评分及MIV评分与肺量测定参数呈负相关。结论：PET/MR能准确评价PCD病变程度。它可以同时评估结构损伤和肺部炎症，两者的结果与肺功能呈负相关。PET/MR是一种很有前途的PCD监测工具。
{"title":"[18F]FDG PET/MR to assess disease extension and inflammation in children and young adults with primary ciliary dyskinesia.","authors":"Silvia Carraro, Valentina A Ferraro, Pietro Zucchetta, Stefania Zanconato, Francesca Serani, Chiara Giraudo, Diego Cecchin","doi":"10.1007/s00259-025-07521-7","DOIUrl":"10.1007/s00259-025-07521-7","url":null,"abstract":"<p><strong>Background: </strong>Primary ciliary dyskinesia (PCD) is a rare condition characterized by ciliary dysfunction, impaired mucociliary clearance and mucus accumulation in the airways.</p><p><strong>Purpose: </strong>Our aim was to evaluate the performance of [18F]FDG PET/MR in assessing structural and inflammatory pulmonary features in patients with PCD, using high-resolution CT (HRCT) as the gold-standard reference.</p><p><strong>Materials and methods: </strong>We recruited patients with PCD (≥ 7 years) regularly followed at our Regional Center for PCD. They underwent chest HRCT and [18F]FDG PET/MR using sequences optimized for the morpho-functional study of the lung. Parametric PET images were obtained by dividing each voxel by the mean value in a reference area. The volume of interest (VOI in cm<sup>3</sup>), named Metabolic Inflammatory Volume (MIV), was calculated by thresholding the PET parametric image using a value twice the mean of the reference area. Standardized Uptake Value (SUV) Max, SUV mean, Total Lesion Glycolysis (TLG) and MIV were recorded. HRCT and MR were analyzed using the Eichinger score.</p><p><strong>Results: </strong>Sixteen patients were enrolled. The Bland-Altman plot showed good agreement between HRCT and MR scores. Cumulative HRCT and MR scores correlated significantly with SUV mean score (HRCT: p = 0.02, r<sub>s</sub>=0.6; MR: p = 0.006, r<sub>s</sub>=0.66) and MIV (HRCT: p = 0.003, r<sub>s</sub> =0.7; MR: p = 0.004, r<sub>s</sub> =0.69). Total HRCT and MR scores and MIV score inversely correlated with spirometric parameters.</p><p><strong>Conclusion: </strong>PET/MR proved to be accurate in evaluating disease extent in PCD. It enabled the simultaneous assessment of structural damage and lung inflammation, both of which resulted inversely related to lung function. PET/MR is a promising tool for PCD monitoring.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"2158-2166"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Purpose: </strong>Somatostatin receptor subtype 2 (SSTR2) is overexpressed in well-differentiated neuroendocrine neoplasms (NENs) and serves as a key target for positron emission tomography (PET) imaging. While SSTR2 agonists such as [<sup>68</sup>Ga]Ga-DOTA-TATE are widely used clinically, recent evidence suggests that antagonist radioligands can bind more receptor sites without inducing internalization, potentially offering superior imaging performance. Here, we report the synthesis, preclinical validation, and pilot clinical translation of [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11, a novel SSTR2 antagonist radioligand featuring an -Asp<sub>2</sub>-PEG<sub>2</sub>- linker designed to enhance hydrophilicity and receptor engagement for PET Imaging of NENs.</p><p><strong>Methods: </strong>Asp<sub>2</sub>-JR11 was synthesized by modifying the NOTA-JR11 backbone, and its binding properties were evaluated via molecular docking, in vitro assays, and in vivo imaging. Radiolabeling with <sup>68</sup>Ga was performed for Asp<sub>2</sub>-JR11, NOTA-JR11, and DOTA-TATE. We conducted cell uptake, internalization, PET/CT imaging, biodistribution, and blocking studies in AR42J (SSTR2-positive) and HCT116 (SSTR2-negative) tumor models. A first-in-human study included nine patients with NENs who underwent [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11 PET/CT and [<sup>18</sup>F]FDG PET/CT imaging, along with dosimetry assessment.</p><p><strong>Results: </strong>Docking analysis showed that Asp<sub>2</sub>-JR11 maintained equivalent binding energy to NOTA-JR11 but formed more hydrogen bonds with SSTR2 (10 vs. 5), suggesting enhanced stability. [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11 demonstrated high radiochemical purity (> 95%), higher molar activity (12.9-14.8 GBq/µmol), and greater hydrophilicity (LogD = - 3.18 ± 0.01) than comparators. In AR42J cells, [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11 exhibited rapid uptake (9.95 ± 0.10%AD/10⁶ cells at 30 min) and low internalization (17.63 ± 0.91% at 120 min), with significantly higher uptake than [<sup>68</sup>Ga]Ga-DOTA-TATE and [<sup>68</sup>Ga]Ga-NOTA-JR11 in both in vitro and micro PET/CT studies (e.g., 10.67 ± 0.16 vs. 7.79 ± 0.50%ID/g at 30 min, p < 0.05). In vivo imaging and biodistribution confirmed higher tumor-to-background ratios and reduced off-target organ uptake, notably in the kidneys, pancreas, and spleen. Tumor uptake was significantly inhibited by co-injection of SSTR2 ligands, confirming specificity. In human subjects, [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11 showed favorable biodistribution and rapid clearance via renal excretion, with the spleen showing the highest transient uptake. Tumors were clearly visualized as early as 12 min post-injection and maintained strong contrast up to 120 min. Dosimetry revealed the highest absorbed dose in the urinary bladder wall (5.78 × 10⁻² mSv/MBq), with an effective whole-body dose of 9.94 × 10⁻³ mSv/MBq. Comparative PET/CT imaging in nine patients (33
{"title":"Synthesis, preclinical evaluation, and clinical translation of [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11, a SSTR2 antagonist for PET imaging of neuroendocrine neoplasms.","authors":"Zihao Chen, Xingyu Mu, Lei Zhang, Zhisheng Jie, Kadeer Tudi, Haoran Liang, Qingxing Liu, Jingze Li, Weixia Chong, Yufeng Mo, Wei Fu, Ganghua Tang","doi":"10.1007/s00259-025-07474-x","DOIUrl":"10.1007/s00259-025-07474-x","url":null,"abstract":"<p><strong>Purpose: </strong>Somatostatin receptor subtype 2 (SSTR2) is overexpressed in well-differentiated neuroendocrine neoplasms (NENs) and serves as a key target for positron emission tomography (PET) imaging. While SSTR2 agonists such as [<sup>68</sup>Ga]Ga-DOTA-TATE are widely used clinically, recent evidence suggests that antagonist radioligands can bind more receptor sites without inducing internalization, potentially offering superior imaging performance. Here, we report the synthesis, preclinical validation, and pilot clinical translation of [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11, a novel SSTR2 antagonist radioligand featuring an -Asp<sub>2</sub>-PEG<sub>2</sub>- linker designed to enhance hydrophilicity and receptor engagement for PET Imaging of NENs.</p><p><strong>Methods: </strong>Asp<sub>2</sub>-JR11 was synthesized by modifying the NOTA-JR11 backbone, and its binding properties were evaluated via molecular docking, in vitro assays, and in vivo imaging. Radiolabeling with <sup>68</sup>Ga was performed for Asp<sub>2</sub>-JR11, NOTA-JR11, and DOTA-TATE. We conducted cell uptake, internalization, PET/CT imaging, biodistribution, and blocking studies in AR42J (SSTR2-positive) and HCT116 (SSTR2-negative) tumor models. A first-in-human study included nine patients with NENs who underwent [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11 PET/CT and [<sup>18</sup>F]FDG PET/CT imaging, along with dosimetry assessment.</p><p><strong>Results: </strong>Docking analysis showed that Asp<sub>2</sub>-JR11 maintained equivalent binding energy to NOTA-JR11 but formed more hydrogen bonds with SSTR2 (10 vs. 5), suggesting enhanced stability. [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11 demonstrated high radiochemical purity (> 95%), higher molar activity (12.9-14.8 GBq/µmol), and greater hydrophilicity (LogD = - 3.18 ± 0.01) than comparators. In AR42J cells, [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11 exhibited rapid uptake (9.95 ± 0.10%AD/10⁶ cells at 30 min) and low internalization (17.63 ± 0.91% at 120 min), with significantly higher uptake than [<sup>68</sup>Ga]Ga-DOTA-TATE and [<sup>68</sup>Ga]Ga-NOTA-JR11 in both in vitro and micro PET/CT studies (e.g., 10.67 ± 0.16 vs. 7.79 ± 0.50%ID/g at 30 min, p < 0.05). In vivo imaging and biodistribution confirmed higher tumor-to-background ratios and reduced off-target organ uptake, notably in the kidneys, pancreas, and spleen. Tumor uptake was significantly inhibited by co-injection of SSTR2 ligands, confirming specificity. In human subjects, [<sup>68</sup>Ga]Ga-Asp<sub>2</sub>-JR11 showed favorable biodistribution and rapid clearance via renal excretion, with the spleen showing the highest transient uptake. Tumors were clearly visualized as early as 12 min post-injection and maintained strong contrast up to 120 min. Dosimetry revealed the highest absorbed dose in the urinary bladder wall (5.78 × 10⁻² mSv/MBq), with an effective whole-body dose of 9.94 × 10⁻³ mSv/MBq. Comparative PET/CT imaging in nine patients (33 ","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"1532-1548"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947501","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 : 2026-01-31DOI: 10.1007/s00259-026-07777-7
Lidia Gatto,Riccardo Mei,Martina Stasolla,Enrico Zuliani,Vincenzo Di Nunno,Alicia Tosoni,Marta Aprile,Stefania Bartolini,Marzia Margotti,Chiara Maria Argento,Stefano Fanti,Enrico Franceschi
PURPOSEPositron emission tomography (PET) has become an increasingly important adjunct to brain MRI in the field of neuro-oncology. PET imaging utilizes radiolabeled tracers, providing in vivo assessment of the metabolic and molecular characteristics of gliomas, thereby providing functional data beyond standard anatomic images. This additional layer of crucial biological insight aids in personalized patient management and treatment decision. In recent years, numerous studies have been carried out for the development and clinical validation of several PET radiotracers in glioma imaging, leading to a substantial improvement in glioma diagnosis, staging, treatment strategy planning as well as in monitoring tumor progression and response to therapy. Ongoing innovations in radiopharmaceutical design have further improved the diagnostic performance of PET by increasing both tracer specificity and tumor detection sensitivity.METHODSIn this review, we summarize recent developments in PET imaging for glioma, with particular emphasis on clinically available amino acid PET tracers. In addition, we provide an overview of emerging theranostic strategies, including peptide receptor radionuclide therapy (PRRT) for meningioma and 177Lu-PSMA-617-based approaches for high-grade glioma.RESULTSThe current guidelines recommend the use of amino acid PET for differentiation of neoplastic from non-neoplastic lesions, for delineation of glioma extent, for non-invasive prediction of molecular information, for grading and prognosis estimation, for differentiation of glioma relapse from treatment-related changes and for the evaluation of treatment response.CONCLUSIONSOverall, this work aims to highlight the role of PET as a complementary imaging modality to MRI and to discuss its potential impact on patient outcomes in neuro-oncological practice.
{"title":"Cutting-edge approaches in pet imaging for gliomas: current applications for neurooncologists and the path to theranostic breakthroughs.","authors":"Lidia Gatto,Riccardo Mei,Martina Stasolla,Enrico Zuliani,Vincenzo Di Nunno,Alicia Tosoni,Marta Aprile,Stefania Bartolini,Marzia Margotti,Chiara Maria Argento,Stefano Fanti,Enrico Franceschi","doi":"10.1007/s00259-026-07777-7","DOIUrl":"https://doi.org/10.1007/s00259-026-07777-7","url":null,"abstract":"PURPOSEPositron emission tomography (PET) has become an increasingly important adjunct to brain MRI in the field of neuro-oncology. PET imaging utilizes radiolabeled tracers, providing in vivo assessment of the metabolic and molecular characteristics of gliomas, thereby providing functional data beyond standard anatomic images. This additional layer of crucial biological insight aids in personalized patient management and treatment decision. In recent years, numerous studies have been carried out for the development and clinical validation of several PET radiotracers in glioma imaging, leading to a substantial improvement in glioma diagnosis, staging, treatment strategy planning as well as in monitoring tumor progression and response to therapy. Ongoing innovations in radiopharmaceutical design have further improved the diagnostic performance of PET by increasing both tracer specificity and tumor detection sensitivity.METHODSIn this review, we summarize recent developments in PET imaging for glioma, with particular emphasis on clinically available amino acid PET tracers. In addition, we provide an overview of emerging theranostic strategies, including peptide receptor radionuclide therapy (PRRT) for meningioma and 177Lu-PSMA-617-based approaches for high-grade glioma.RESULTSThe current guidelines recommend the use of amino acid PET for differentiation of neoplastic from non-neoplastic lesions, for delineation of glioma extent, for non-invasive prediction of molecular information, for grading and prognosis estimation, for differentiation of glioma relapse from treatment-related changes and for the evaluation of treatment response.CONCLUSIONSOverall, this work aims to highlight the role of PET as a complementary imaging modality to MRI and to discuss its potential impact on patient outcomes in neuro-oncological practice.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"143 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088926","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}
PURPOSELong axial field of view (LAFOV) PET imaging requires extensive automation due to the large number of target tissues. Therefore, we introduce an open-source analysis pipeline (TurBO, Turku total-BOdy) for automated preprocessing and kinetic modelling of LAFOV [15O]H2O and [18F]FDG PET data. TurBO enables efficient, reproducible quantification of tissue perfusion and metabolism at regional- and voxel-levels through automated co-registration, motion correction, CT-based region of interest (ROI) segmentation, image-derived input function (IDIF) extraction, and region-specific kinetic modelling.METHODSThe pipeline was validated with Biograph Vision Quadra (Siemens Healthineers) LAFOV PET/CT data from 21 subjects scanned with [15O]H2O and 16 subjects scanned with [18F]FDG. Six CT-segmented ROIs (cortical brain gray matter, left iliopsoas muscle, right kidney cortex and medulla, pancreas, spleen and liver) were used to assess different levels of tissue perfusion and glucose metabolism.RESULTSModel fits showed high quality with consistent estimates at regional and voxel-levels (R2 > 0.83 for [15O]H2O, R2 > 0.99 for [18F]FDG). Manual and automated IDIFs were in concordance (R2 > 0.74 for [15O]H2O, and R2 > 0.78 for [18F]FDG) with minimal bias (< 4% and < 10%, respectively). Manual and CT-segmented ROIs showed strong agreement (R2 > 0.82 for [15O]H2O and R2 > 0.83 for [18F]FDG). Motion correction had little impact on estimates (R2 > 0.71 for [15O]H2O and R2 > 0.78 for [18F]FDG) compared with uncorrected data.CONCLUSIONThe TurBO pipeline provides fully automated and reliable quantification for LAFOV PET data. It substantially reduces manual workload and enables standardized, reproducible assessment of inter-organ perfusion and metabolism.
{"title":"Automated long axial field of view PET image processing and kinetic modelling with the TurBO toolbox.","authors":"Jouni Tuisku,Santeri Palonen,Henri Kärpijoki,Aino Latva-Rasku,Nelli Tuomola,Harri Harju,Sergey V Nesterov,Vesa Oikonen,Hidehiro Iida,Jarmo Teuho,Chunlei Han,Tomi Karjalainen,Anna K Kirjavainen,Johan Rajader,Riku Klén,Pirjo Nuutila,Juhani Knuuti,Lauri Nummenmaa","doi":"10.1007/s00259-026-07769-7","DOIUrl":"https://doi.org/10.1007/s00259-026-07769-7","url":null,"abstract":"PURPOSELong axial field of view (LAFOV) PET imaging requires extensive automation due to the large number of target tissues. Therefore, we introduce an open-source analysis pipeline (TurBO, Turku total-BOdy) for automated preprocessing and kinetic modelling of LAFOV [15O]H2O and [18F]FDG PET data. TurBO enables efficient, reproducible quantification of tissue perfusion and metabolism at regional- and voxel-levels through automated co-registration, motion correction, CT-based region of interest (ROI) segmentation, image-derived input function (IDIF) extraction, and region-specific kinetic modelling.METHODSThe pipeline was validated with Biograph Vision Quadra (Siemens Healthineers) LAFOV PET/CT data from 21 subjects scanned with [15O]H2O and 16 subjects scanned with [18F]FDG. Six CT-segmented ROIs (cortical brain gray matter, left iliopsoas muscle, right kidney cortex and medulla, pancreas, spleen and liver) were used to assess different levels of tissue perfusion and glucose metabolism.RESULTSModel fits showed high quality with consistent estimates at regional and voxel-levels (R2 > 0.83 for [15O]H2O, R2 > 0.99 for [18F]FDG). Manual and automated IDIFs were in concordance (R2 > 0.74 for [15O]H2O, and R2 > 0.78 for [18F]FDG) with minimal bias (< 4% and < 10%, respectively). Manual and CT-segmented ROIs showed strong agreement (R2 > 0.82 for [15O]H2O and R2 > 0.83 for [18F]FDG). Motion correction had little impact on estimates (R2 > 0.71 for [15O]H2O and R2 > 0.78 for [18F]FDG) compared with uncorrected data.CONCLUSIONThe TurBO pipeline provides fully automated and reliable quantification for LAFOV PET data. It substantially reduces manual workload and enables standardized, reproducible assessment of inter-organ perfusion and metabolism.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"103 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088927","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 : 2026-01-30DOI: 10.1007/s00259-025-07737-7
Brett W Sperry,Eric Burgett,James A Case,Timothy M Bateman
{"title":"Rapid dynamic acquisition of cardiac amyloid radionuclide imaging.","authors":"Brett W Sperry,Eric Burgett,James A Case,Timothy M Bateman","doi":"10.1007/s00259-025-07737-7","DOIUrl":"https://doi.org/10.1007/s00259-025-07737-7","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"261 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072923","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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