European Journal of Nuclear Medicine and Molecular Imaging最新文献

{"title":"Assessing the frequency and accuracy of morphologic changes of focal bone lesions on [⁶⁸Ga]Ga-PSMA-11 PET/CT in prostate cancer.","authors":"Thibika Sivakumar, Jakob Heimer, Stephan Beintner-Skawran, Urs J Muehlematter, Michael Messerli, Noel Spielhofer, Daniel Eberli, Martin W Huellner, Irene A Burger, Alexander Maurer","doi":"10.1007/s00259-025-07331-x","DOIUrl":"https://doi.org/10.1007/s00259-025-07331-x","url":null,"abstract":"<p><strong>Background: </strong>In [¹⁸F]F-PSMA-1007 PET imaging, focal bone uptake without morphological correlate (MC) on CT, is often classified as benign. In [⁶⁸Ga]Ga-PSMA-11, intense focal uptake without MC in a classical location is considered suspicious. The prevalence of focal bone uptake with or without MC on [⁶⁸Ga]Ga-PSMA-11 PET/CT remains unclear.</p><p><strong>Methods: </strong>This single-center, retrospective study included patients who underwent a [⁶⁸Ga]Ga-PSMA-11 PET/CT scan for initial staging or biochemical recurrence (BCR) of prostate cancer between 04/16 - 11/21, with written informed consent for use of clinical data and adequate follow-up. For each patient with focal PSMA accumulation in the bones, up to three of these lesions were scored based on PSMA-RADS 2.0 and a clinical interpretation of suspicion for malignancy including clinical information was provided. In addition, MC on CT were assessed. A composite reference standard including imaging and clinical follow-up data was used.</p><p><strong>Results: </strong>Out of 824 patients, 323 met eligibility criteria, with 101 showing PSMA-positive bone lesions. 176 lesions were included, 25% of 61 in the staging cohort had no MC, of which 73% were malignant. In the BCR group, 52% of 115 lesions were without MC, of which 48% were malignant. The sensitivity/specificity reached with PSMA-RADS 2.0, and MC on CT was 100%/100%and 78%/36% for staging, and 83%/100% and 60%/72% for BCR, respectively.</p><p><strong>Conclusion: </strong>Focal [⁶⁸Ga]Ga-PSMA-11 positive lesions without MC on CT are frequent, especially on scans for BCR, with the majority being malignant. Considering PSMA-RADS 4 lesions on [⁶⁸Ga]Ga-PSMA-11 on staging exams, significantly improves the accuracy. Incorporating clinical information and considering PSMA-RADS 3B can further improve the sensitivity for BCR scans.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309768","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":"The additive value of 68Ga-RM26 PET/CT to 68Ga-PSMA-617 PET/CT in assessing Post-treatment outcomes of ARSIs in mCRPC patients.","authors":"Xuhao Liu,Lin Qi,Xiaomei Gao,Shuo Hu,Yongxiang Tang,Minfeng Chen,Yi Cai","doi":"10.1007/s00259-025-07407-8","DOIUrl":"https://doi.org/10.1007/s00259-025-07407-8","url":null,"abstract":"BACKGROUNDBesides its potential as a PET/CT tracer, the Gastrin-Releasing Peptide Receptor (GRPR) has been shown to predict the prognosis of Prostate Cancer (PCa). Herein, we aimed to evaluate the additive ability of 68Ga-RM26 PET/CT as a tracer to predict the prognosis of patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) following Androgen Receptor Signal Inhibitors (ARSIs) therapy.METHODSThis retrospective single-center study involved patients who underwent both 68Ga-PSMA-617 PET/CT and 68Ga-RM26 PET/CT scans. Based on the GRPR status of their lesions (positive/negative), the patients were stratified into two cohorts, and their actual prognosis was assessed by comparing their maximum Prostate-Specific Antigen (PSA) response rates and Progression-Free Survival (PFS) durations following ARSI therapy.RESULTSThis study involved 44 patients. Among them, 41 and 23 showed PSMA uptake and GRPR uptake, respectively, with 3 exhibiting GRPR uptake alone. The GRPR + group had an median PSA response rate of 37.78% and a median PFS duration of 8.9 months, both of which were significantly lower than those of GRPR- patients, whose corresponding values were 69.39% and 14.37 months, respectively. According to the multivariate analysis results, GRPR status, distant Lymph Node Metastasis (LNM) and PSMA SUVmax of bone metastases lesions were significant predictors of the PSA response rate. Furthermore, the GRPR status and PSMA SUVmax of regional lymph node metastases were significant predictors of PFS.CONCLUSIONCompared to GRPR- patients, mCRPC patients with GRPR + lesions exhibited a lower median maximum PSA response rate and a shorter median PFS duration following ARSI treatment, implying a poorer response to therapy and relatively worse prognosis in the latter subgroup.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"36 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295756","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":"Native Ligand-Inspired peptides for c-MET targeted PET probes development.","authors":"Renli Luo,Boyu Tan,Ying Zhang,Jing Hu,Jia Lin,Luming Sun,Xiaonan Wei,Nianting Ju,Xiangning Luo,Chuan Chen,Junyu Bao,Ji Tao,Yanting Qu,Chunrong Qu,Renda Li,Yuanpeng Jiang,Quanyong Luo,Rui Cao,Zhen Cheng","doi":"10.1007/s00259-025-07403-y","DOIUrl":"https://doi.org/10.1007/s00259-025-07403-y","url":null,"abstract":"PURPOSENative ligand-derived peptides have significantly advanced the development of targeting ligands in radiopharmaceutical discovery and design. Herein, we report the first attempt to develop novel mesenchymal-epithelial transition factor (c-MET) targeted peptide positron emission tomography (PET) probes based on the endogenous biomolecule, hepatocyte growth factor (HGF).METHODSThree c-MET targeted peptides were designed from the N-terminal and kringle 1 domain (NK1: 32-207 amino acid residues) of HGF. Then they were conjugated with chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled with [68Ga]GaCl3. The resulted [68Ga]Ga-labelled probes, [68Ga]Ga-DOTA-K1, [68Ga]Ga-DOTA-A-C5, and [68Ga]Ga-DOTA-A-M8 were evaluated in vitro and in vivo.RESULTSAmong three PET probes, [68Ga]Ga-DOTA-A-M8 exhibited a high affinity for c-MET (IC50 = 5.43 nM) and demonstrated specific and high uptake in c-MET highly expressing HCT-116 cells. Small animal PET/CT imaging clearly visualized the tumor with good contrast using [68Ga]Ga-DOTA-A-M8 over 120 min. Quantitative analysis of PET images revealed tumor uptake of [68Ga]Ga-DOTA-A-M8 at 30 min post-injection was 2.91 ± 0.20%ID/g in HCT-116 models. The probe was mainly cleared out through the kidney-bladder pathway. Biodistribution study showed HCT-116 tumor uptake of 2.84 ± 0.07%ID/g and 0.54 ± 0.09%ID/g in the normal and blocking mice group, respectively, at 30 min post-injection. The tumor-to-muscle, tumor-to-blood and tumor-to-liver ratios were 3.60 ± 1.09, 1.48 ± 0.24 and 2.48 ± 0.28, respectively, at 30 min.CONCLUSIONA novel c-MET-targeting PET probe, [68Ga]Ga-DOTA-A-M8, has been successfully developed in this study. It demonstrates high tumor-targeting capability and specificity. This study highlights developing PET probes based on native ligands is a powerful and generalizable strategy.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"598 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295754","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":"Divergent prognostic utility of metabolic risk scores in large B-cell lymphoma subtypes: a real-world analysis.","authors":"Vibeke K J Vergote,Gregor Verhoef,Ann Janssens,F J S Woei-A-Jin,Wies Deckers,Annouschka Laenen,Thomas Tousseyn,Daan Dierickx,Christophe M Deroose","doi":"10.1007/s00259-025-07368-y","DOIUrl":"https://doi.org/10.1007/s00259-025-07368-y","url":null,"abstract":"PURPOSELarge B-cell lymphomas (LBCL) include diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), and subtypes such as transformed non-Hodgkin's lymphoma (tNHL), primary mediastinal B-cell lymphoma (PMBL), and double/triple-hit lymphomas (DHL/THL). While metabolic risk scores based on metabolic tumor volume (MTV) have demonstrated prognostic value in DLBCL, NOS, their applicability to other LBCL subtypes remains unclear.METHODSBaseline [18F]FDG-PET/CT scans of LBCL patients treated with R-CHOP regimens at our institution were retrospectively analyzed. Metabolic parameters, including MTV, lesion dissemination (SDmax) and tumor surface volume ratio were calculated for each histological subgroup. Four metabolic risk scores-the international metabolic prognostic index (IMPI), MTV/WHO PS, MTV/SDmax and Clinical PET model- were applied to calculate progression risk in LBCL subtypes. Harrell's C-index evaluated the prognostic performance. A multivariable model was developed for tNHL.RESULTSWe included tNHL (n = 88), DHL/THL (n = 32), PMBL (n = 26) and others (n = 49), and compared them to a cohort of previously published DLBCL, NOS (n = 355). IMPI demonstrated the highest C-index amongst the metabolic risk scores in tNHL for progression-free survival (PFS), overall survival, time to progression and progression of disease within 12 months, but was outperformed by the IPI. For DHL/THL the highest C-indices were observed for MTV/WHO PS. For PMBL the clinical PET score showed the highest C-indices. SDmax improved prognostic predictions in PMBL and tNHL, but not in DHL/THL. Multivariate analysis identified independent predictors of PFS in tNHL, including IPI and SUVmean.CONCLUSIONMetabolic risk scores show variable prognostic value across LBCL subtypes. Subtype-specific metabolic models may enhance personalized risk stratification and guide treatment approaches.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"10 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295755","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":"Image reconstruction and analysis of atherosclerosis imaging by [¹⁸F]FDG PETCT using digital PET technology.","authors":"Stephen Rankin, A J Gemmell, J McClure, B Venugopal, P J Slomka, M C Petrie, N N Lang, D Colville, Alexander Small","doi":"10.1007/s00259-025-07345-5","DOIUrl":"https://doi.org/10.1007/s00259-025-07345-5","url":null,"abstract":"<p><strong>Purpose: </strong>Digital PETCT scanners have improved spatial resolution and sensitivity. This may have implications for reconstruction parameters and atherosclerosis assessment using [¹⁸F]FDG. On a contemporary digital scanner, we assessed European Association of Nuclear Medicine's (EANM)-recommended reconstruction parameters and blood pool methods, compared with a locally-optimised protocol using fewer iterations and subsets than recommended by EANM.</p><p><strong>Methods: </strong>Using clinical PETCT and phantom analysis, we quantitatively assessed two reconstructions ('EANM' and 'local') for atherosclerotic assessment using mean contrast recovery (MCR), absolute error and coefficient of variation (CoV). We assessed the impact of each reconstruction on tissue-to-background ratio (TBR). We also assessed the differences within four blood pool regions on repeated imaging over 24-weeks.</p><p><strong>Results: </strong>EANM reconstruction yielded higher TBRmax, 4.28 ± 0.65 vs 1.81 ± 0.24 p < 0.0001, than local reconstruction. Phantom data demonstrated a higher RCmax curve with EANM vs local reconstruction. EANM MCR was 1.87 vs 1.23 with local reconstruction, with higher absolute error (2.23 vs 0.61) and variation (7.63% vs 4.14%), vs local reconstruction. Superior vena cava (SVC) offered the most reproducible and reliable blood pool data. Internal jugular vein had lower FDG-uptake compared to other regions, resulting in higher TBRmax, but was less reproducible between scans over 24 weeks.</p><p><strong>Conclusion: </strong>Local reconstruction, with fewer iterations and subsets compared to EANM recommendations, resulted in more accurate atherosclerotic assessment on a contemporary digital scanner. Metrics for assessing reconstructions, such as absolute error and CoV, provided valuable information. The blood pool region used affects TBR. SVC appears to provide the most reliable blood pool region.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293571","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":"Clinical and molecular correlates of limbic age-related TDP-43 encephalopathy (LATE) ¹⁸F-FDG-PET pattern in amnestic mild cognitive impairment.","authors":"Cecilia Boccalini, Luisa Knappe, Gregory Mathoux, Debora Elisa Peretti, Federica Ribaldi, Francesca B Pizzini, Linjing Mu, Max Scheffler, Giovanni B Frisoni, Valentina Garibotto","doi":"10.1007/s00259-025-07395-9","DOIUrl":"https://doi.org/10.1007/s00259-025-07395-9","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283054","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":"[⁶⁸Ga]Ga-DOTA-TOC positron emission tomography outperforms [¹⁸F]FDOPA and [¹⁸F]FDG PET in pediatric neuroblastoma imaging: a prospective study.","authors":"Chia-Ju Liu, Kuan-Yin Ko, Meng-Yao Lu, Wan-Ting Hung, Shu-Wei Chou, Chia-Jui Du, Hsiu-Hao Chang, Wen-Ming Hsu, Yung-Li Yang, Yu-Ting Chien, Steven Shinn-Forng Peng, Mei-Fang Cheng","doi":"10.1007/s00259-025-07399-5","DOIUrl":"https://doi.org/10.1007/s00259-025-07399-5","url":null,"abstract":"<p><strong>Purpose: </strong>Neuroblastoma is a heterogeneous pediatric malignancy with variable imaging characteristics. Neuroblastoma tumors express SSTR receptors, but the role of [⁶⁸Ga]Ga-DOTA-TOC in neuroblastoma remains unclear. This study aimed to compare the diagnostic accuracy of [⁶⁸Ga]Ga-DOTA-TOC PET against [¹⁸F]FDOPA PET and [¹⁸F]FDG PET in neuroblastoma.</p><p><strong>Methods: </strong>Patients with histologically confirmed neuroblastoma were prospectively recruited between September 2021 and September 2024. All participants underwent PET imaging using three radiotracers. Each modality was assessed for lesion detectability. Bone lesions were evaluated using the SIOPEN system. PET findings were interpreted as true lesions following multidisciplinary tumor board discussions and confirmed with follow-up imaging. Detectability across modalities was compared using Cochran's Q test, while maximal standardized uptake values (SUVmax) were analyzed using repeated measures ANOVA and post hoc pairwise comparisons.</p><p><strong>Results: </strong>Fifteen patients (mean age 6.1 ± 3.4; 6 females and 9 males) underwent paired PET imaging using three different radiotracers, predominantly stage M (13/15 patients) and high risk (14/15 patients). In patient-based analysis, [¹⁸F]FDG PET failed to detect active disease in two patients, resulting in a detection rate of 86.7% (13/15), while [⁶⁸Ga]Ga-DOTA-TOC and [¹⁸F]FDOPA PET successfully identified all patients (15/15, 100%). A total of 203 lesions were identified in the lesion-based analysis. [⁶⁸Ga]Ga-DOTA-TOC PET demonstrated superior detectability (199/203 lesions, 98.0%), compared to [¹⁸F]FDOPA PET (129/203, 63.5%) and [¹⁸F]FDG PET (122/203, 60.1%) (p < 0.001). SUVmax was highest for [⁶⁸Ga]Ga-DOTA-TOC PET (5.5 ± 4.0), followed by [18F]FDG PET (1.8 ± 1.4) and [¹⁸F]FDOPA PET (0.6 ± 0.5) (p < 0.001). Organ-based analysis revealed that [⁶⁸Ga]Ga-DOTA-TOC provides superior detection rates in lymph node (55/57, 96.5%), soft tissue (43/43, 100%), bone and bone marrow (89/89, 100%) metastases. SUVmax was generally higher on [⁶⁸Ga]Ga-DOTA-TOC PET/CT for both primary lesions and metastases (all p < 0.001), except in the liver. The majority of lesions (170/203, 83.7%) exhibited a Krenning score of 2 or higher.</p><p><strong>Conclusion: </strong>The enrichment of somatostatin receptors in neuroblastoma makes [⁶⁸Ga]Ga-DOTA-TOC PET a highly effective detection tool compared to [¹⁸F]FDOPA PET and [¹⁸F]FDG PET. A multimodal imaging approach can enhance disease evaluation and guide personalized therapeutic strategies, potentially facilitating radioligand therapy.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283053","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":"Ending nuclear weapons, before they end us.","authors":"Kamran Abbasi, Parveen Ali, Virginia Barbour, Marion Birch, Inga Blum, Peter Doherty, Andy Haines, Ira Helfand, Richard Horton, Kati Juva, Jose F Lapena, Robert Mash, Olga Mironova, Arun Mitra, Carlos Monteiro, Elena N Naumova, David Onazi, Tilman Ruff, Peush Sahni, James Tumwine, Carlos Umaña, Paul Yonga, Chris Zielinski","doi":"10.1007/s00259-025-07365-1","DOIUrl":"https://doi.org/10.1007/s00259-025-07365-1","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283055","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":"Fibroblast activation protein-targeted PET/CT in multiple non-ischemic cardiomyopathies.","authors":"Qiao Yang, Song Xue, Chao Ren, Xue Lin, Marcus Hacker, Wei Chen, Na Niu, Xiang Li, Li Huo","doi":"10.1007/s00259-025-07385-x","DOIUrl":"https://doi.org/10.1007/s00259-025-07385-x","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274512","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":"Impact of white matter hyperintensities on α4β2 nicotinic acetylcholine receptor binding in the human brain.","authors":"Michael Rullmann, Philipp M Meyer, Andreas Schildan, Karl-Titus Hoffmann, Osama Sabri, Solveig Tiepolt","doi":"10.1007/s00259-025-07383-z","DOIUrl":"https://doi.org/10.1007/s00259-025-07383-z","url":null,"abstract":"<p><strong>Purpose: </strong>White matter hyperintensities (WMHs) are commonly observed in aging and neurodegenerative diseases, but their impact on the α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) system remains unclear. This study investigates the relationship between WMHs and gray matter nicotinic signaling, aiming to elucidate potential pathways contributing to neurodegeneration.</p><p><strong>Methods: </strong>Multimodal imaging data using PET and MR imaging from 39 participants, including 19 healthy controls and 20 patients with Alzheimer's disease dementia (AD), were analyzed. WMHs were identified on T1-weighted MPRAGE and T2-weighted TSE MR images using advanced segmentation algorithms. Probabilistic fiber tracking was applied to determine WMH-connected gray matter. PET-based total distribution volume (V_T) values of the α4β2-nAChR tracer (-)-[¹⁸F]Flubatine were compared between WMH-affected and unaffected gray matter regions.</p><p><strong>Results: </strong>WMH volumes were significantly correlated with age, Fazekas and MMSE scores, but no differences in absolute or relative WMH volumes were observed between healthy controls and patients with AD. PET-based V_T values in WMH-connected gray matter showed no significant difference from contralateral unaffected regions, regardless of disease status or WMH burden. However, intra-individual differences in V_T values correlated with Fazekas scores, presumably driven by patients with AD. Pathway-based analyses revealed decreased V_T values in the medial cholinergic pathway of patients with AD but no significant differences in lateral pathways.</p><p><strong>Conclusion: </strong>This study shows that WMHs do not significantly alter gray matter nicotinic signaling in directly connected regions. However, the results suggest subtle associations between WMH severity and specific cholinergic pathways, particularly in AD.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265659","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}