European Journal of Nuclear Medicine and Molecular Imaging最新文献

{"title":"Quantification of monoamine oxidase B expression with 11C-SL25.1188 for imaging reactive astrocytes in patients with Alzheimer's disease.","authors":"Kiwamu Matsuoka,Yuhei Takado,Yasuyuki Kimura,Akihiko Kitamura,Hitomi Kitamura,Mayuka Kanda,Michihiro Takada,Maiko Ono,Harutsugu Tatebe,Hironobu Endo,Shin Kurose,Keisuke Takahata,Yoko Ikoma,Masanori Ichihashi,Masaki Oya,Kosei Hirata,Hideki Matsumoto,Asumi Orihara,Naomi Kokubo,Yuko Kataoka,Hong Zhang,Kenji Tagai,Chie Seki,Hitoshi Shinotoh,Tatsuya Kikuchi,Masanori Ichise,Hiroshi Shimizu,Akiyoshi Kakita,Kazunori Kawamura,Ming-Rong Zhang,Hitoshi Shimada,Kenji Nagao,Takahiko Tokuda,Makoto Higuchi","doi":"10.1007/s00259-025-07542-2","DOIUrl":"https://doi.org/10.1007/s00259-025-07542-2","url":null,"abstract":"PURPOSEAstrocyte reactivation can be assessed using positron emission tomography (PET) ligands targeting monoamine oxidase B (MAO-B). 11C-SL25.1188 binds reversibly to MAO-B, allowing precise density measurements, but requires invasive arterial sampling. This study aimed to develop a simplified, noninvasive method to quantify MAO-B with 11C-SL25.1188 PET in Alzheimer's disease (AD).METHODSSix patients with mild cognitive impairment (MCI), five patients with AD, and six healthy controls (HCs) underwent 11C-SL25.1188 PET scans. The distribution volume ratios (DVRs) were calculated and compared using two methods: the original multilinear reference tissue model (MRTMO) and the Logan plot. Changes in MAO-B densities, plasma glial fibrillary acidic protein (GFAP) levels, and abnormal protein aggregation were examined among subjects.RESULTSA strong agreement was observed between the DVRs estimated using MRTMO and those obtained with the Logan plot (r2 = 0.89), with the cerebellar cortex used as the reference region. This region was selected based on its similar total distribution volume values and comparable MAO-B levels between patients with AD and HCs. Patients with MCI showed higher DVRs in the parietal cortex compared to those with moderate AD. Moreover, patients with moderate AD had higher plasma GFAP levels than HCs but similar levels to patients with MCI.CONCLUSIONMAO-B density in patients with MCI/AD can be accurately estimated by calculating DVRs using a simplified quantification method that does not require arterial blood sampling. The estimated MAO-B density shows an increase that peaks at the MCI stage, suggesting early astrocyte reactivation in the progression of AD pathology.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"62 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003287","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}

{"title":"Artificial intelligence-assisted assessment of metabolic response to tebentafusp in metastatic uveal melanoma: a long axial field-of-view [18F]FDG PET/CT study.","authors":"Christos Sachpekidis,Devayani Machiraju,Dimitrios Stefanos Strauss,Leyun Pan,Annette Kopp-Schneider,Lars Edenbrandt,Antonia Dimitrakopoulou-Strauss,Jessica C Hassel","doi":"10.1007/s00259-025-07504-8","DOIUrl":"https://doi.org/10.1007/s00259-025-07504-8","url":null,"abstract":"PURPOSETebentafusp has emerged as the first systemic therapy to significantly prolong survival in treatment-naïve HLA-A*02:01 + patients with unresectable or metastatic uveal melanoma (mUM). Notably, a survival benefit has been observed even in the absence of radiographic response. This study aims to investigate the feasibility and prognostic value of artificial intelligence (AI)-assisted quantification and metabolic response assessment of [18F]FDG long axial field-of-view (LAFOV) PET/CT in mUM patients undergoing tebentafusp therapy.MATERIALS AND METHODSFifteen patients with mUM treated with tebentafusp underwent [18F]FDG LAFOV PET/CT at baseline and 3 months post-treatment. Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were quantified using a deep learning-based segmentation tool On the RECOMIA platform. Metabolic response was assessed according to AI-assisted PERCIST 1.0 criteria. Associations between PET-derived parameters and overall survival (OS) were evaluated using Kaplan-Meier survival analysis.RESULTSThe median follow up (95% CI) was 14.1 months (12.9 months - not available). Automated TMTV and TLG measurements were successfully obtained in all patients. Elevated baseline TMTV and TLG were significantly associated with shorter OS (TMTV: 16.9 vs. 27.2 months; TLG: 16.9 vs. 27.2 months; p < 0.05). Similarly, higher TMTV and TLG at 3 months post-treatment predicted poorer survival outcomes (TMTV: 14.3 vs. 24.5 months; TLG: 14.3 vs. 24.5 months; p < 0.05). AI-assisted PERCIST response evaluation identified six patients with disease control (complete metabolic response, partial metabolic response, stable metabolic disease) and nine with progressive metabolic disease. A trend toward improved OS was observed in patients with disease control (24.5 vs. 14.6 months, p = 0.08). Circulating tumor DNA (ctDNA) levels based on GNAQ and GNA11 mutations were available in 8 patients; after 3 months Of tebentafusp treatment, 5 showed reduced Or stable ctDNA levels, and 3 showed an increase (median OS: 24.5 vs. 3.3 months; p = 0.13). Patients with increasing ctDNA levels exhibited significantly higher TMTV and TLG on follow-up imaging.CONCLUSIONAI-assisted whole-body quantification of [1⁸F]FDG PET/CT and PERCIST-based response assessment are feasible and hold prognostic significance in tebentafusp-treated mUM. TMTV and TLG may serve as non-invasive imaging biomarkers for risk stratification and treatment monitoring in this malignancy.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"163 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002800","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}

{"title":"Effect of bone marrow disease on hematologic toxicity and response to [177Lu]Lu-PSMA-617 therapy: insights from PSMA-PET/CT imaging.","authors":"Nuno Borges,Meryam Losee,Mofei Liu,Su-Chun Cheng,Arda Könik,Jolivette Ritzer,Andrew Wolanski,Thomas S C Ng,Atish D Choudhury,Mary-Ellen Taplin,Praful Ravi,Heather Jacene","doi":"10.1007/s00259-025-07541-3","DOIUrl":"https://doi.org/10.1007/s00259-025-07541-3","url":null,"abstract":"PURPOSEDespite the effectiveness of [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC), hematologic toxicity remains a concern, particularly in patients with bone metastases. This study evaluated whether the extent, intensity, and heterogeneity of bone disease on pretreatment PSMA-PET/CT were associated with hematologic toxicity, PSA response, and overall survival (OS) in mCRPC patients treated with [177Lu]Lu-PSMA-617.METHODSThis retrospective study included 96 mCRPC patients who underwent pretreatment PSMA-PET/CT and received standard-of-care [177Lu]Lu-PSMA-617. Hematologic toxicity, PSA responses, and OS were analyzed in relation to quantitative PET parameters, including tumor volume, SUVmean, and heterogeneity of PSMA uptake in bone metastases.RESULTSClinically significant hematologic toxicity occurred in 19 patients (19.8%). Treatment discontinuation was more likely in those with a significantly higher (p = 0.007) percentage of total bone volume with PSMA-avid disease (median 28% vs. 1.7%). Those requiring dose delays or reductions (median 21% vs. 1.5%), blood transfusions (median 21% vs. 1.4%), and platelet transfusions (median 32% vs. 1.8%) also exhibited higher median percentages of total bone volume involvement (all p < 0.01). Patients with more heterogeneous PSMA uptake had lower PSA50 response rates than those with more homogeneous uptake (30.3% vs. 64.5%, p = 0.002). A > 50% difference between PSMA-low and PSMA-high bone disease was associated with significantly shorter OS (p < 0.001).CONCLUSIONExtensive PSMA-avid bone involvement was associated with increased hematologic toxicity in mCRPC treated with [177Lu]Lu-PSMA-617. Greater heterogeneity in PSMA uptake correlated with lower PSA50 response and OS but not hematologic toxicity. Careful patient selection and monitoring are needed, particularly in those with widespread bone disease.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"64 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995912","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}

{"title":"Sentinel node detection and imaging concordance in Early-Stage ovarian cancer: A MELISA trial analysis of tracer, timing, and intraoperative gamma camera.","authors":"Nuria Agusti,Pilar Paredes,Sergi Vidal-Sicart,Federico Migliorelli,Cristina Celada,Nuria Carreras,Francisco Campos,Tiermes Marina,Inmaculada Romero,Ariel Glickman,Andrea Fritsch,Nahir Navarro,Pere Fuste,Aureli Torne,Berta Diaz-Feijoo","doi":"10.1007/s00259-025-07535-1","DOIUrl":"https://doi.org/10.1007/s00259-025-07535-1","url":null,"abstract":"PURPOSETo evaluate the detection rate of sentinel lymph node (SLN) mapping in early-stage ovarian cancer using [99mTc]Tc-nanocolloid and indocyanine green (ICG), and the added value of an intraoperative gamma camera.METHODSThis was a prospective single-center trial of 63 patients with suspected early-stage epithelial ovarian cancer who underwent SLN mapping with combined tracers. [99mTc]Tc-nanocolloid was injected into the ovarian ligaments before adnexectomy, and if malignancy was confirmed on intraoperative frozen section, ICG was administered after adnexectomy in immediate staging cases. SLNs were identified using a handheld gamma probe, the gold standard, and a portable gamma camera for radiotracer localization, alongside near-infrared imaging for ICG. We calculated SLN detection rates for each tracer and concordance between the tracers (reflecting the impact of injection timing), including identification of the same SLN- as well as between detection modalities. Cohen's κ and PABAK were used to assess concordance between detection modalities. Patients with confirmed malignancy underwent complete pelvic and aortic lymphadenectomy.RESULTSAmong 63 patients, sentinel lymph nodes (SLNs) were detected in 79.4% using [99mTc]Tc-nanocolloid. In the 30 patients who also received ICG, the combined use of both tracers achieved a detection rate of 93.3%, with higher detection in the aortic region compared to the pelvic region (83.3% vs. 43.3%). The intraoperative gamma camera showed 83.3% concordance with the gamma probe, including 87.5% concordance in the aortic region and 66.7% in the pelvic region. Among patients who received both tracers, 14 had drainage in at least one region by both, and 12 of these (85.7%) showed concordant detection of the same SLN. Concordance was 100% in re-staging and 77.8% in immediate surgeries.CONCLUSIONSLN mapping in ovarian cancer using a dual tracer approach is feasible and yields a higher detection rate than single tracers. The gamma camera identified SLN localization mainly in aortic regions. This combination may improve nodal staging in early ovarian cancer and reduce the need for systematic lymphadenectomy. Post-adnexectomy injection is a practical alternative to injection before adnexectomy for immediate surgeries, although caution is needed due to potential variations in lymphatic drainage.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"33 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995883","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}

{"title":"Cranial glucose metabolic patterns across prodromal and clinical parkinson's disease revealed by ¹⁸F-FDG PET.","authors":"Weizhao Lu, Tianbin Song, Ying Zhou, Qiaoling Zeng, Jing Li, Bixiao Cui, Jie Lu","doi":"10.1007/s00259-025-07533-3","DOIUrl":"10.1007/s00259-025-07533-3","url":null,"abstract":"<p><strong>Purpose: </strong>Bone plays pivotal roles in glucose homeostasis of the human body. Parkinson's disease (PD) is accompanied by metabolic dysfunction and increased risks of bone diseases. Nevertheless, whether PD affects bone glucose metabolism remains unknown. This study aimed to assess cranial glucose metabolism in different stages of PD using brain ¹⁸F-fludeoxyglucose positron emission tomography (¹⁸F-FDG PET).</p><p><strong>Methods: </strong>This prospective cross-sectional study included 190 participants, including 34 controls, 32 prodromal PD (pPD), 50 de novo PD (dnPD) and 74 medicated PD (mPD) patients. mPD patients were further separated into 3 stages: early-, middle- and late-stage PD patients. Comparisons of glucose uptake in the cranium was assessed using general linear model among controls, pPD, dnPD and mPD patients, as well as among mPD patients with different stages. Furthermore, effects of motor function, disease duration and dopaminergic medication on cranial glucose uptake were assessed using multiple linear regression.</p><p><strong>Results: </strong>The results demonstrated cranial hypermetabolism in clinically confirmed PD patients (dnPD and mPD patients) compared to HCs in the cranium, frontal, sphenoid and parietal bones (p < 0.05). In addition, mPD patients also demonstrated hypermetabolism in temporal and occipital bones compared to HCs (p < 0.05). However, this metabolic pattern was not observed in the prodromal individuals. Moreover, multiple linear regression identified fasting blood glucose as a positive modulator (β = 0.020 ~ 0.043, p < 0.05) and dopaminergic medication as a negative regulator (β=-1.207 × 10^-4~-9.482 × 10^-5, p < 0.005) of cranial glucose metabolic activity.</p><p><strong>Conclusion: </strong>The current study uncovered cranial metabolic abnormalities in PD, offering new perspectives and pathophysiological insights underlying bone-related comorbidities in PD.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947192","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}

{"title":"Association of PET vascular activity score with Takayasu's arteritis angiographic progression.","authors":"Sifan Wu, Bing Wu, Lingying Ma, Mengdi Li, Xianting Sun, Shuhui Zhang, Hongcheng Shi, Lindi Jiang","doi":"10.1007/s00259-025-07348-2","DOIUrl":"10.1007/s00259-025-07348-2","url":null,"abstract":"<p><strong>Objective: </strong>Arterial wall Fluorodeoxyglucose (FDG) uptake can reflect vascular inflammation in Takayasu's arteritis (TAK); however, its association with vascular prognosis remains unclear. This study assessed the predictive efficacy of the PET vascular activity score (PETVAS) for vascular prognosis and whether FDG uptake in specific arterial territories was associated with angiographic progression in TAK.</p><p><strong>Methods: </strong>Patients with TAK from a prospective observational cohort who underwent ¹⁸F-FDG PET/CT and serological tests at baseline were included. Magnetic Resonance Angiography and/or Contrast-Enhanced Ultrasound were conducted at baseline and every six months during follow-up. The PETVAS was calculated. New/aggravated lesions were considered as angiographic progression.</p><p><strong>Results: </strong>The imaging evaluation included 1,353 arterial territories from 123 patients. The baseline PETVAS was positively correlated with Erythrocyte Sedimentation Rate (ESR), serum IL-6, and Platelet. Angiographic progression was noted in 45 patients (36.6%) with 72 territories (5.3%) during 30 (18-72) months of follow-up. Of these, 19 (42.2%) had baseline PETVAS > 15, including 84.2% (16/19) naïve cases and 78.9% (15/19) with ESR ≥ 30 mm/h. Multivariate Cox proportional hazards regression analysis adjusted for age and sex showed baseline PETVAS > 15 (HR 1.93; 95% CI, 1.01-3.68; p = 0.04) an independent predictor of angiographic progression.</p><p><strong>Conclusion: </strong>Baseline PETVAS > 15 was an independent predictor of angiographic progression in TAK. Baseline FDG uptake in specific arterial territories did not correlate with vascular progression. Our study provides a feasible PET/CT-based predictive marker for vascular progression in TAK and underscores the importance of regular imaging follow-up to monitor disease outcomes.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"4268-4280"},"PeriodicalIF":7.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157509","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}

{"title":"Distinguishing benign lesions from malignant ones using FAPI-based tracers: will we need to bid farewell to dual-time points imaging?","authors":"Priscilla Guglielmo, Laura Evangelista","doi":"10.1007/s00259-025-07254-7","DOIUrl":"10.1007/s00259-025-07254-7","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"3935-3937"},"PeriodicalIF":7.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810870","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}

{"title":"PET imaging of TREM2 in amyloid-beta induced neuroinflammation.","authors":"Amelia D Dahlén, Sahar Roshanbin, Ximena Aguilar, Nadja M Bucher, Sara Lopes van den Broek, Dag Sehlin, Stina Syvänen","doi":"10.1007/s00259-025-07358-0","DOIUrl":"10.1007/s00259-025-07358-0","url":null,"abstract":"<p><strong>Purpose: </strong>The triggering receptor expressed on myeloid cells 2 (TREM2) has become a promising target for biologics in both monitoring and treating neuroinflammation in Alzheimer's disease (AD). This study aimed to develop and compare bispecific anti-TREM2 antibodies featuring different transferrin receptor (TfR) binders to enhance brain delivery, identifying the most suitable format for in vivo PET imaging of TREM2 in transgenic AD mice.</p><p><strong>Methods: </strong>Three bispecific TREM2-antibody formats were produced and evaluated for their ability to cross the blood-brain barrier (BBB) via TfR-mediated transcytosis and bind TREM2. Blood concentration profiles up to 72 h post-injection (p.i.), and ex vivo brain uptake of iodine-125-labeled antibody constructs were quantified in App^NL-G-F and age-matched wild type (WT) mice using a γ-counter. The best-performing bispecific TREM2-antibody was radiolabeled with iodine-124 and used for in vivo PET imaging of brain TREM2 levels in App^NL-G-F mice at 72 h p.i. Brain TREM2 concentrations were subsequently quantified using ELISA.</p><p><strong>Results: </strong>The antibody format carrying two scFv8D3 TfR-binders (IgG-scFv₂), demonstrated the highest brain concentrations of all tested bispecific constructs. This antibody also exhibited significantly higher brain concentrations in App^NL-G-F mice compared to WT mice at both 48 and 72 h p.i. This difference was further visualized and quantified through in vivo PET imaging. Moreover, brain concentrations of the antibody ligand correlated with elevated TREM2 levels in brain homogenates.</p><p><strong>Conclusion: </strong>These findings highlight IgG-scFv₂ as a promising radioligand for in vivo PET imaging of TREM2, advancing non-invasive neuroinflammation studies and supporting drug development for AD and other neurodegenerative diseases.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"4320-4333"},"PeriodicalIF":7.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157564","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}

{"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":"https://doi.org/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 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.</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_s=0.6; MR: p = 0.006, r_s=0.66) and MIV (HRCT: p = 0.003, r_s =0.7; MR: p = 0.004, r_s =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":""},"PeriodicalIF":7.6,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, preclinical evaluation, and clinical translation of [⁶⁸Ga]Ga-Asp₂-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":"https://doi.org/10.1007/s00259-025-07474-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;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 [&lt;sup&gt;68&lt;/sup&gt;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 [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-Asp&lt;sub&gt;2&lt;/sub&gt;-JR11, a novel SSTR2 antagonist radioligand featuring an -Asp&lt;sub&gt;2&lt;/sub&gt;-PEG&lt;sub&gt;2&lt;/sub&gt;- linker designed to enhance hydrophilicity and receptor engagement for PET Imaging of NENs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Asp&lt;sub&gt;2&lt;/sub&gt;-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 &lt;sup&gt;68&lt;/sup&gt;Ga was performed for Asp&lt;sub&gt;2&lt;/sub&gt;-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 [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-Asp&lt;sub&gt;2&lt;/sub&gt;-JR11 PET/CT and [&lt;sup&gt;18&lt;/sup&gt;F]FDG PET/CT imaging, along with dosimetry assessment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Docking analysis showed that Asp&lt;sub&gt;2&lt;/sub&gt;-JR11 maintained equivalent binding energy to NOTA-JR11 but formed more hydrogen bonds with SSTR2 (10 vs. 5), suggesting enhanced stability. [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-Asp&lt;sub&gt;2&lt;/sub&gt;-JR11 demonstrated high radiochemical purity (&gt; 95%), higher molar activity (12.9-14.8 GBq/µmol), and greater hydrophilicity (LogD = - 3.18 ± 0.01) than comparators. In AR42J cells, [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-Asp&lt;sub&gt;2&lt;/sub&gt;-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 [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-TATE and [&lt;sup&gt;68&lt;/sup&gt;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 &lt; 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, [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-Asp&lt;sub&gt;2&lt;/sub&gt;-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":""},"PeriodicalIF":7.6,"publicationDate":"2025-08-30","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}