Nuclear medicine and biology最新文献

{"title":"Drying free strategies for sustainable fluorine-18 radiochemistry","authors":"Nektarios Pirmettis ,&nbsp;Alexandros Pappas ,&nbsp;Sevban Doğan Ekici ,&nbsp;Abdul Karim Haji Dheere ,&nbsp;Charalampos Triantis ,&nbsp;Ioannis Pirmettis ,&nbsp;Antonio Shegani","doi":"10.1016/j.nucmedbio.2026.109611","DOIUrl":"10.1016/j.nucmedbio.2026.109611","url":null,"abstract":"<div><div>Azeotropic removal of water remains a significant limitation in fluorine-18 radiochemistry, often leading to longer synthesis times, variable yields, increased solvent use and operational complexity, and, indirectly, increased resource demand due to decay- and loss-driven activity requirements and incompatibility with base- or heat-sensitive precursors. This review critically evaluates drying-free strategies that mitigate or obviate this step while sustaining high radiochemical performance and compliance with good manufacturing practice. Methods are organized into controlled hydrous fluorination, ionic-liquid media, mixed organic solvent systems, alcohol-assisted elution, copper-mediated aromatic radiofluorination, rhenium-complexation routes, and other advanced approaches. Comparative analysis addresses fluoride recovery, radiochemical yield, substrate scope, including electron-rich arenes and base-sensitive chemotypes, tolerance to residual water/alcohol, cycle time, solvent and waste metrics, and suitability for automation and clinical translation. Copper-mediated protocols currently provide broad aromatic coverage with competitive yields under minimally basic, non-dried conditions; alcohol-assisted and mixed-solvent systems offer rapid, cassette-ready workflows for many aliphatic targets; and rhenium-assisted labeling enables mild conditions for sensitive scaffolds. Remaining challenges include standardized reagent kits and quality control, management of residual metals or additives, harmonized sustainability metrics, and consistent implementation across synthesis platforms. Collectively, drying-free strategies support more robust, streamlined and resource-efficient ¹⁸F tracer synthesis and are poised to facilitate scalable production and wider clinical adoption.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109611"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-column derivatization high-performance liquid chromatography-ultraviolet-ultraviolet (HPLC-UV) method for the detection of Kryptofix 2.2.2 content in Positron Emission Tomography (PET) tracers","authors":"Lei Xu ,&nbsp;Zhenhao Dong ,&nbsp;Hong Zhang ,&nbsp;Antonio Arleques Gomes ,&nbsp;Wagner de Rossi ,&nbsp;Jing Wang ,&nbsp;Arian Pérez Nario ,&nbsp;Qinggang He","doi":"10.1016/j.nucmedbio.2026.109610","DOIUrl":"10.1016/j.nucmedbio.2026.109610","url":null,"abstract":"<div><div>A post-column derivatization high-performance liquid chromatography-ultraviolet (HPLC-UV) method was developed to determine Kryptofix 2.2.2 (K2.2.2) in PET tracers. This method utilizes the specific complexation between K2.2.2 and Pb²⁺, forming a stable 1:1 host-guest complex. The complexation produces a bathochromic shift in UV absorption maximum (from 210 nm to 254 nm), enabling sensitive detection. This approach addresses the limitations of poor performance and narrow applicability associated with direct single-method detection of K2.2.2.</div><div>The chromatographic conditions were optimized (column flow rate: 0.7 mL·min⁻¹; derivatization reagent flow rate: 0.7 mL·min⁻¹; Pb²⁺ concentration: 50 μg·mL⁻¹) and the method was validated. The results exhibited excellent linearity (1–100 μg·mL⁻¹, r² &gt; 0.999), high reproducibility (relative standard deviation (RSD) &lt; 5%), and a low detection limit (0.5 μg·mL⁻¹). The method successfully quantified K2.2.2 in [¹⁸F]FDG, [¹⁸F]AV45 and [¹⁸F]DPA714, achieving spiked recoveries of 89%–105%. Additionally, the method remained unaffected by interference from common sample components such as sodium chloride and sodium ascorbate.</div><div>This method provides a novel and efficient quality control tool for the simultaneous analysis of radiochemical purity and K2.2.2 content in diverse PET tracers.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109610"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesothelin-targeted alpha therapy in PDAC with [225Ac]Ac-Macropa-PEG6-Amatuximab","authors":"Syed Qaiser Shah ,&nbsp;Ralph Santos-Oliveira ,&nbsp;Madeeha Shabnam ,&nbsp;DeryaIlem-Ozdemir","doi":"10.1016/j.nucmedbio.2026.109606","DOIUrl":"10.1016/j.nucmedbio.2026.109606","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) continues to be deadly and resistant to traditional treatments. Overexpressed in &gt;80% of PDACs, mesothelin is an ideal target for antibody-based α-therapy. Actinium-225 (225Ac) produces high-LET α-particles leading to irreparable DNA damage, but its utility has been compromised by unstable chelation with traditional ligands. Here, we engineered a Macropa-enabled, site-specifically [²²⁵Ac]Ac-Macropa-PEG₆-Amatuximab, a radioimmunoconjugate against mesothelin. Conjugation and labeling were characterized by MALDI-TOF and SEC-HPLC. In vitro stability, immunoreactivity, and kinetics of binding were tested in mesothelin-positive AsPC-1 cells and subsequently in vivo biodistribution, dosimetry, and therapy in AsPC-1 xenograft-bearing nude mice. Conjugation had an average ratio of 3.6 ± 0.1 for chelator per antibody, radiolabeling efficiency of 96.3 ± 1.1%, and radiochemical purity ≥98%. The radioconjugate was &gt;92% stable after 168 h in serum, with immunoreactivity (82.2 ± 2.8%) and affinity (Kd = 4.3 ± 0.9 nM). It exhibited specific, time-dependent internalization in AsPC-1 cells and minimal nonspecific uptake. In vivo, [²²⁵Ac]Ac-Macropa-PEG₆-Amatuximab exhibited prolonged circulation, specific tumor localization (3.9 ± 0.5 to 16.3 ± 2.1% ID/g, 1–168 h), and enhanced tumor-to-blood ratios (0.21–3.40). Blocking with unlabeled Amatuximab decreased tumor uptake by &gt;60%. The tumor absorbed dose (1.82 ± 0.14 Gy/MBq) was 4–20-fold greater than doses to normal organs. Therapeutically, it caused dose-dependent tumor regression (TGI: 58% at 50 kBq; 92% at 150 kBq) and prolonged survival (&gt;60 days vs. 0–1% in controls, <em>p</em> &lt; 0.001). [²²⁵Ac]Ac-Macropa-PEG₆-Amatuximab is stable, selective, and therapeutically effective, demonstrating Macropa-based 225Ac chelation as a stable platform for targeted α-therapy of PDAC.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"154 ","pages":"Article 109606"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetic modelling and evaluation of the TrkA/B/C radioligand [18F]TRACK in the pig brain","authors":"Cassis Varlow ,&nbsp;Clara A. Madsen ,&nbsp;Carolin Jaworski ,&nbsp;Gjertrud Louise Laurell ,&nbsp;Vladimir Shulganov ,&nbsp;Jane Skjøth-Rasmussen ,&nbsp;Arafat Nasser ,&nbsp;Ralf Schirrmacher ,&nbsp;Gitte M. Knudsen","doi":"10.1016/j.nucmedbio.2025.109600","DOIUrl":"10.1016/j.nucmedbio.2025.109600","url":null,"abstract":"<div><div>Tropomyosin receptor kinase B (TrkB) is a critical mediator of neuronal growth, survival, and synaptic plasticity, which is activated by the endogenous ligand, brain-derived neurotrophic factor (BDNF). TrkB has been implicated in a wide range of neurological conditions, including neurodegenerative, psychiatric, and proliferative disorders. Non-invasive imaging of TrkB using positron emission tomography (PET) has been pursued to enhance understanding of its role in disease and support therapeutic development. Here, we investigated the <em>in vitro</em> and <em>in vivo</em> properties of [¹⁸F]TRACK, a fluorine-18 labeled radioligand for TrkB, in pig brain and human glioblastoma tissue.</div><div>Autoradiography revealed high specific binding of [¹⁸F]TRACK in both pig brain and glioblastoma biopsy samples, suggesting robust target engagement. <em>In vivo</em> PET imaging in pigs demonstrated moderate brain uptake (peak standardized uptake value of 1.2), widespread cortical distribution, and slow washout. Kinetic modelling favored the two-tissue compartment model (2TCM) for quantification. Despite high <em>in vitro</em> specificity, within-scan displacement with the TrkB antagonist ANA-12 failed to produce measurable changes in tracer binding, indicating a need for further validation of <em>in vivo</em> specificity. Moreover, both <em>in vivo</em> and <em>in vitro</em>, [¹⁸F]TRACK binding was consistently highest in the white matter. These findings encourage a continued search for novel molecular neuroimaging radioligands to image TrkB in disease models and humans.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109600"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of concern \"cross sections of the 226Ra(p,xn) reactions relevant for 225Ac production\".","authors":"","doi":"10.1016/j.nucmedbio.2025.109598","DOIUrl":"10.1016/j.nucmedbio.2025.109598","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152-153 ","pages":"109598"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recovery of zinc-68 from gallium-68 cyclotron target effluent: A method to establish wet chemistry capabilities for metal precursor recovery in PET radiometals","authors":"Ian M. Horn ,&nbsp;Anna C. Bitzer ,&nbsp;Patrick L. Day ,&nbsp;Mark S. Jacobson ,&nbsp;Jeffrey M. McEarchern","doi":"10.1016/j.nucmedbio.2025.109582","DOIUrl":"10.1016/j.nucmedbio.2025.109582","url":null,"abstract":"<div><h3>Background</h3><div>Gallium-68 (68Ga) is a PET isotope that is finding more use in the clinical setting as a PET diagnostic tool, e.g. 68Ga PSMA is widely used in the diagnosis of prostate cancer, and 68Ga dotatate for the diagnosis of neuroendocrine tumors. Current production is mostly performed using either germanium-68/gallium-68 (68Ge/68Ga) generators or liquid targets containing zinc-68 (68Zn) and irradiated with protons in an accelerator. Recently, GE Healthcare published an article describing the production and purification of 68Ga using solid 68Zn target irradiation. The method described in this study to recover 68Zn from liquid target effluent may also be used to re-purify 68Zn from effluents from 68Ga production using solid targets. Preliminary studies, to be published in a follow-up paper, that result in electroplated solid 68Zn targets are briefly mentioned to demonstrate that such targets can be made from the 68Zn purified using this recovery method.</div></div><div><h3>Method</h3><div>An ion-exchange based method was used for purifying (or ‘recovering’) target material-containing effluent for future reuse in target preparation. This was accomplished using a column with Bio-Rad AG1-X8 resin bed of approximately 20–25 g of resin in a glass ion-exchange column. Eluted fractions from the ion-exchange column were tested using a NexION 350D ICP-MS to detect the presence of total zinc and trace contaminants Cu, Fe, Pb, Cr, Al, Mn, Ti, Ni, and Ag. The isotopic purity of the 68Zn in the effluent was also measured to confirm the original isotopic ratio.</div></div><div><h3>Results</h3><div>The results presented indicate that any contaminants in the effluent samples were reduced to levels below the limits of detection of analytical techniques commonly used in PET manufacturing laboratories (including ICP-OES).</div></div><div><h3>Conclusion</h3><div>This article provides a simple method for recovering 68Zn from liquid target effluent to be used in the plating of 68Zn targets for 68Ga solid target production. This method will allow academic/PET facilities to establish a wet chemistry process for recovering 68Zn and, using separation schemes published or developed elsewhere, and other precursors used for making solid cyclotron targets for isotope production.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109582"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMB Innovators Series Professor Yasuhisa Fujibayashi, PhD, DMedSci","authors":"Takako Furukawa ,&nbsp;Yasuhisa Fujibayashi ,&nbsp;Charles Metzger","doi":"10.1016/j.nucmedbio.2026.109609","DOIUrl":"10.1016/j.nucmedbio.2026.109609","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109609"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S0969-8051(26)00018-1","DOIUrl":"10.1016/S0969-8051(26)00018-1","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109619"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147394848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET evaluation of cholinergic system differences in progressive supranuclear palsy and age-matched controls using [18F]VAT","authors":"Ying-Hwey Nai ,&nbsp;John L. O’Donnell ,&nbsp;Aaron Tanenbaum ,&nbsp;Anil Kumar Soda ,&nbsp;Hao Jiang ,&nbsp;Stephen M. Moerlein ,&nbsp;Scott A. Norris ,&nbsp;Joel S. Perlmutter ,&nbsp;Zhude Tu","doi":"10.1016/j.nucmedbio.2025.109599","DOIUrl":"10.1016/j.nucmedbio.2025.109599","url":null,"abstract":"<div><h3>Background</h3><div>The availability of binding sites for the vesicular acetylcholine transporter (VAChT) provides a measure of presynaptic cholinergic neuron terminals, which undergo degeneration in various conditions, including progressive supranuclear palsy (PSP). We used a VAChT-specific PET radiotracer, [¹⁸F]VAT, to determine whether the density of cholinergic terminals in PSP differs from that of cognitively intact healthy controls (HC). We further performed the analysis using the standardized uptake value ratio (SUVR) and partial volume correction (PVC) methods. Nine clinically diagnosed PSP participants (72 ± 8 years, 5 M/4F) and twenty sex- and age-matched HC (71 ± 8 years,12 M/8 F) had a 120-min dynamic [¹⁸F]VAT-PET scan. Distribution volume ratios (DVR) from Logan graphical analysis and SUVR were generated with eroded cerebral white matter as the reference region using the region of interest (ROI)-based approach. Spearman correlations between SUVR and DVR with clinical measurements, namely the Montreal Cognitive Assessment (MoCA), disease duration, and Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III), were investigated. Statistical analysis was performed using the Mann-Whitney <em>U</em> test, with significance defined at <em>p</em> &lt; 0.05. The data were corrected for multiple comparisons for target regions of caudate, putamen, accumbens, and entorhinal cortex, and without multiple comparisons for other ROIs in exploratory analysis.</div></div><div><h3>Results</h3><div>Significant reduction of &gt;9 % in DVR and SUVR values was observed in PSP in the entorhinal cortex (FDR-corrected <em>p</em> ≤ 0.023), while significant reduction of &gt;10 % in the DVR values only was observed in the caudate (FDR-corrected <em>p</em> = 0.044). Exploratory analyses suggested that PSP patients had lower DVR and SUVR values in thalamus, hippocampus, caudal anterior cingulate, isthmus cingulate, lateral occipital cortex, lingual, pars orbitalis, pericalcarine, posterior cingulate, superior temporal, supramarginal, and transverse temporal regions compared to HCs. Exploratory analyses also revealed that DVR and SUVR of the brainstem correlated with disease duration (|ρ| &gt; 0.877, <em>p</em> ≤ 0.003), whereas DVR and SUVR of the ventral diencephalon and brainstem correlated with MoCA scores (|ρ| &gt; 0.48, <em>p</em> ≤ 0.008). No region correlated with UPDRS-III. SUVR (100-120 min) correlated well with DVR. PVC did not improve correlations with clinical measures.</div></div><div><h3>Conclusions</h3><div>Lower [¹⁸F]VAT relates to lower cognitive function; further studies with an increased sample size could strengthen the justification for cholinergic treatment approaches to target cognitive decline in PSP.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109599"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating [11C]methylreboxetine PET and MRI to map in vivo norepinephrine transporter distribution: A proof-of-concept study of noradrenergic vulnerability in neurodegeneration","authors":"Jaime D. Mondragon ,&nbsp;Sofia Marcolini ,&nbsp;Bruno Lima Giacobbo ,&nbsp;Philip H. Elsinga ,&nbsp;Rudi A.J.O. Dierckx ,&nbsp;Marleen Tollenaere ,&nbsp;Debby van Dam ,&nbsp;Peter P. De Deyn","doi":"10.1016/j.nucmedbio.2025.109581","DOIUrl":"10.1016/j.nucmedbio.2025.109581","url":null,"abstract":"<div><h3>Background</h3><div>The locus coeruleus (LC) and its noradrenergic projections are among the earliest sites displaying pathology in Alzheimer's disease (AD) and Parkinson's disease (PD). In vivo measures of norepinephrine transporter (NET) availability with [¹¹C]methylreboxetine ([¹¹C]MRB) positron emission tomography (PET) and structural magnetic resonance imaging (MRI) indices of LC integrity provide complementary, but rarely integrated biomarkers.</div></div><div><h3>Methods</h3><div>13 Healthy controls (HC), individuals with 12 AD or amnestic mild cognitive impairment due to AD (AD/aMCI), and 5 patients with PD underwent [¹¹C]MRB PET and high-resolution T1-weighted MRI. NET availability was quantified using [¹¹C]MRB PET SUV-ratio–based binding potential (SUVr-BP) in the LC and projection regions (hippocampus, amygdala, thalamus, and prefrontal cortex). LC structural integrity was indexed by LC MRI contrast-to-noise ratio (CNR), and projection region volumes were extracted with FreeSurfer. Group differences were assessed with Kruskal–Wallis tests, and PET–MRI associations were examined using Pearson correlations with Yeo–Johnson transformation to reduce outlier influence.</div></div><div><h3>Results</h3><div>No significant group-level differences in [¹¹C]MRB PET SUVr-BP or MRI measures were observed across HC, AD/aMCI, and PD. However, LC [¹¹C]MRB PET SUVr-BP correlated with LC MRI-CNR (<em>r</em> = 0.429, 95 % CI [0.082–0.684], <em>p</em> = 0.018). In contrast, PET–MRI associations in projection regions were weak and non-significant. Exploratory analyses confirmed expected differences in cognition, neuropsychiatric symptoms, and functional measures, most pronounced in AD/aMCI participants.</div></div><div><h3>Conclusions</h3><div>This proof-of-concept study demonstrates convergent multimodal assessment of LC integrity using [¹¹C]MRB PET and LC MRI-CNR, whereas projection regions showed divergent or absent associations. These findings highlight the potential of the LC as a target for multimodal biomarker development and support further investigation of these imaging strategies in larger, longitudinal cohorts to delineate their role in detecting noradrenergic vulnerability in neurodegeneration.</div></div><div><h3>Significance statement</h3><div>This study integrates [¹¹C]MRB PET and MRI to examine noradrenergic integrity in Alzheimer's and Parkinson's disease. Results demonstrate strong PET–MRI convergence in the locus coeruleus, but not in projection regions, highlighting the locus coeruleus as a sensitive biomarker target and supporting multimodal imaging approaches for early detection of neurodegenerative vulnerability.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109581"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}