Molecular Imaging and Biology最新文献

{"title":"Enhanced Visualisation of Colorectal Tumours via Topical Application of EMI-137 in a Methylcellulose-Based Formulation: An ex vivo Feasibility Study.","authors":"Elham Zonoobi, Daan G J Linders, Stefan Harmsen, María Rita Rodríguez Luna, Shadhvi S Bhairosingh, Dima D A Almandawi, Ronald L P Van Vlierberghe, Marvin W J Nogaitzig, Christophe Portal, Stijn A L P Crobach, Michele Diana, Gilbert Noordam, Davey van den Burg, Elke E M Peters, Andreas W K S Marinelli, Rob A E M Tollenaar, Denise E Hilling, Peter J K Kuppen, Alexander L Vahrmeijer","doi":"10.1007/s11307-025-02042-z","DOIUrl":"10.1007/s11307-025-02042-z","url":null,"abstract":"<p><strong>Background: </strong>Fluorescence-guided molecular imaging may improve colorectal cancer (CRC) patient outcomes by enabling early detection and better surgical treatment, relying on developing targeted fluorescent tracers to highlight tumours. This study investigates visualising primary colon tumours by topically applying EMI-137, a targeted fluorescent tracer designed to bind to c-Met receptor. We introduce a novel viscous formulation to enhance the tracer's performance, aiming for a clear, robust fluorescent signal by improving contact with mucosal surface of ex vivo colon specimens.</p><p><strong>Methods: </strong>We evaluated fluorescence properties of EMI-137 in phosphate-buffered saline (PBS) and in methylcellulose (m-cellulose) and determined emission spectrum of the tracer in both formulations. Flow cytometry was used to determine EMI-137's specificity for c-Met receptor and its optimal concentration. Live-cell imaging visually confirmed EMI-137's fluorescence signal for the c-Met receptor, highlighting its distinctive characteristics across various solvents. In a prospective cohort study, freshly excised colon cancer specimens were incubated with EMI-137 in PBS or m-cellulose. Specimens underwent a meticulous washing process. Near-infrared fluorescence imaging was performed and compared with histopathological analysis to validate detection accuracy.</p><p><strong>Results: </strong>Fluorospectrometry showed that m-cellulose enhanced EMI-137's fluorescence intensity compared to PBS. Flow cytometry showed dose-dependent binding of EMI-137 in HT-29 cells, with an optimum at 500 nM. Microscopy confirmed targeting of c-Met receptors. Topical EMI-137 dissolved in m-cellulose visualised colon tumours effectively, resulting in a high tumour-to-background ratio. Histopathological analysis confirmed c-Met expression in these colon tumours.</p><p><strong>Conclusion: </strong>EMI-137 in a novel viscous vehicle effectively imaged c-Met expressing colon tumors, potentially facilitating fluorescent-guided tumor imaging.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874178","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":"Evaluation of Indocyanine Green Derivatives with Sulfonic Acid and Carboxylic Acid Groups at the Benzoindolenine Moiety for Antibody-Based Tumor Imaging.","authors":"Kohei Nakajima, Hirotaka Maeta, Hideo Takakura, Koki Tsuchiya, Takayuki Ohira, Mikako Ogawa","doi":"10.1007/s11307-025-02041-0","DOIUrl":"https://doi.org/10.1007/s11307-025-02041-0","url":null,"abstract":"<p><strong>Purpose: </strong>In target-specific cancer imaging, antibodies and their fragments are conjugated with fluorescent dyes to work as targeting molecules. We have recently developed indocyanine green (ICG) derivatives with anionic functional groups at the benzoindolenine moiety. When the ICG derivatives are used for antibody-based imaging, the chemical characteristics of the conjugated dyes may influence the pharmacokinetics of the targeting molecules. Therefore, in this study, we evaluated the in vivo pharmacokinetics of IgG and Fab conjugated with the ICG derivatives bearing anionic functional groups.</p><p><strong>Procedures: </strong>A linker for conjugation was introduced into the methine chain of ICG and ICG derivatives possessing sulfonic acid (SC-Cy) or carboxylic acid (CC-Cy) groups at the benzoindolenine moiety. ICG, SC-Cy, or CC-Cy was conjugated with IgG, innate trastuzumab, and its Fab fragment. To evaluate the pharmacokinetics of these IgG-dyes and Fab-dyes, in vivo fluorescence imaging was performed in tumor-bearing mice at 0.25-96 h after intravenous administration of the imaging agents.</p><p><strong>Results: </strong>The three IgG-dyes exhibited similar pharmacokinetics and tumor accumulation profiles post injection. Thus, the differences in the dye's chemical properties had minimal influence when the ICG derivatives were conjugated with IgG. In contrast, the pharmacokinetics and tumor accumulation profiles of the Fab-dyes were remarkably different. While Fab-SC-Cy exhibited high accumulation in the kidney but no accumulation in the tumors, Fab-CC-Cy showed higher tumor accumulation. This could be attributed to the excessively high negative charge density in the benzoindolenine moiety of SC-Cy, which influenced the excretion route of the Fab fragment.</p><p><strong>Conclusions: </strong>The IgG conjugated with SC-Cy or CC-Cy dyes exhibited favorable pharmacokinetics profiles. In contrast, Fab-CC-Cy demonstrated superior performance in tumor imaging compared to Fab-SC-Cy. Our findings suggest that introducing anionic functional groups into the benzoindolenine moiety of ICG could lead to the development of near-infrared dyes that could be useful in antibody-based tumor imaging.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835770","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 Imaging of Diabetes-Induced Alterations in Metabolism and Immune Activation.","authors":"Shannon E Lynch, Heba M Alsheikh, Patrick N Song, Candace C Parker, Yujun Zhang, Clayton C Yates, Benjamin M Larimer, Suzanne E Lapi, Lalita A Shevde, Anna G Sorace","doi":"10.1007/s11307-025-02027-y","DOIUrl":"10.1007/s11307-025-02027-y","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity and type 2 diabetes (T2D) influence the tumor microenvironment by altering glucose metabolism, which has been shown to decrease immune cell infiltration and activation. Positron emission tomography (PET) imaging provides a non-invasive method to detect molecular markers of immune populations in the tumor microenvironment and systemic organs. The goal of this study is to utilize advanced molecular imaging to quantify differences in innate and adaptive immune responses in diabetic obese mice systemically and within the tumor microenvironment.</p><p><strong>Methods: </strong>5-6-week-old female C57BL6/J mice were placed on a high-fat diet (HFD) composed of 60% kcal fat or control low-fat diet with 10% kcal fat. Animals were treated with subsequent low doses of streptozotocin to induce T2D and blood glucose was monitored. Following induction of diabetes, E0771-luc + cells were implanted into the 4th mammary fat pad and allowed to grow to a tumor volume of 100mm³. PET imaging was acquired over the course of 5 days with the following tracers: [¹⁸F]-FDG PET for glucose metabolism, [⁶⁸Ga]Ga-RP832c (CD206) PET for M2 macrophages, and [⁶⁸Ga]Ga-GZP PET for granzyme B, an indicator of effector cell activation, and [¹⁸F]-DPA-714 PET for neuroinflammation. Regions of interest were identified for the tumor, brain, kidneys, heart, muscle, brown adipose tissue (BAT), to characterize differences in important organs and tumor tissue. Metrics of standardized uptake value (SUV) were extracted from imaging data including mean, max, peak, and tumor-to-background ratios. Following the final imaging timepoint, tumors were extracted for biological characterization via flow cytometry.</p><p><strong>Results: </strong>Diabetic obese mice have no difference in tumor glucose metabolism, but have decreased FDG uptake in the brain and BAT compared to controls. Obesity and T2D systemically affect innate and adaptive immune infiltration and activation including significantly increased RP832c and GZP in muscle, heart, brain, and BAT. Hyperglycemic tumors had trending decreases in GZP SUV_mean and increased RP832c SUV_mean. Flow cytometry shows diabetic obese tumors have a significant increase in CD206 + macrophages and no significant difference in GZB + CD8 + T cells compared to controls.</p><p><strong>Conclusion: </strong>PET imaging reveals that obesity and T2D alter glucose metabolism and immune activation while suppressing tumor-immune activation in diabetic obese mice both within the tumor microenvironment and systemically.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835771","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":"Fibrotic Disease: from Signaling Pathways and Biomarkers to Molecular Imaging.","authors":"Mobin Ghazaiean, Patrick J Riss, Alireza Mardanshahi, Sajjad Molavipordanjani","doi":"10.1007/s11307-025-02038-9","DOIUrl":"https://doi.org/10.1007/s11307-025-02038-9","url":null,"abstract":"<p><p>Fibrotic diseases are characterized by excessive accumulation of extracellular matrix (ECM) components following tissue injury, ultimately leading to organ dysfunction and failure. The progression of fibrosis is governed by complex molecular signaling pathways, including TGF-β, PDGF, FGF, CTGF, VEGF, and many others, which regulate myofibroblast activation, ECM production, and tissue remodeling. Traditional diagnostic modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and biopsy are limited in their ability to distinguish active fibrogenesis from established fibrosis or detect early molecular changes. Recent advances in molecular imaging such as the development of targeted radiotracers and MRI contrast agents-have enabled more precise detection and characterization of fibrotic processes at both preclinical and clinical levels. The integration of molecular imaging with targeted probes holds promise for improving early diagnosis, guiding therapeutic strategies, and advancing clinical management of fibrosis. This review presents a comprehensive overview of the molecular mechanisms underlying fibrogenesis, highlights key signaling pathways and biomarkers, and discusses current and emerging molecular imaging agents for fibrotic diseases diagnosis and monitoring.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822024","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":"CREBBP Mutation as a Culprit for Negative SSTR2 PET in Neuroendocrine Tumors.","authors":"Arvin Haj-Mirzaian, Shadi A Esfahani, Umar Mahmood, Pedram Heidari","doi":"10.1007/s11307-025-02040-1","DOIUrl":"https://doi.org/10.1007/s11307-025-02040-1","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate the molecular and genetic factors contributing to negative ⁶⁸Ga-DOTATATE PET imaging in neuroendocrine tumors (NETs). By integrating whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq), we sought to unravel the interplay between negative results of ⁶⁸Ga-DOTATATE PET and genetic mutations in NETs.</p><p><strong>Methods: </strong>A total of 18 patients with lung, ileal, or pancreatic NETs who underwent ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT scans as part of their initial diagnostic workup were retrospectively reviewed. WES analysis was conducted to investigate the genetic profile of circulating tumor cells of patients with negative ⁶⁸Ga-DOTATATE scans. Leveraging scRNA-seq and single-cell somatic variant calling analysis, we compared the mutation burden and genetic hallmarks of NET cells with high /positive SSTR2 expression to those with negative/low SSTR2 expression.</p><p><strong>Results: </strong>Our analysis identified an association between negative ⁶⁸Ga-DOTATATE scans and reduced survival rates, regardless of tumor grade. WES highlighted a predominance of missense mutations, including CREBBP mutation, particularly in patients with negative PET results (incidence of %67 vs. %0). We observed a deleterious mutation in the SSTR2, likely accounting for the observed negative PET scans (incidence of %33). Single-cell single nucleotide variant (SNV) analysis showed that the total unique mutation burden in cells with negative/low SSTR2 expression was significantly higher compared to cells with positive/high expression; and notably, the CREBBP mutation was observed in more than 50% of patients and approximately 35% of NET cells. These results indicate that the frequency of CREBBP mutations is nearly as high as other well-known NET mutations such as MEN1, PTEN, and RB1. Additionally, CREBBP mutations are significantly more frequent in tumors with negative/low SSTR2 expression.</p><p><strong>Conclusion: </strong>This study suggests that CREBBP mutations in NETs may potentially alter SSTR2 expression, indicating that patients with the mutated CREBBP genotype may not be suitable candidates for SSTR2-targeted PET imaging and radionuclide therapy.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799660","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":"Reengineered Anti-CD4 Cys-diabody Variants for ⁸⁹Zr-immunoPET of CD4⁺ T Cells in Immunocompetent Mice.","authors":"Felix B Salazar, Richard Tavaré, Arya Ökten, Maciej Kujawski, Anna M Wu, Kirstin A Zettlitz","doi":"10.1007/s11307-025-02043-y","DOIUrl":"https://doi.org/10.1007/s11307-025-02043-y","url":null,"abstract":"<p><strong>Purpose: </strong>CD4⁺ T cells (T helper and T reg) play an important role in the immune system and are influential in autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) and cancer (antitumor immunity). Non-invasive, whole-body anti-CD4 immunoPET can provide dynamic and spatial information (localization, proliferation, and migration) on CD4⁺ T cells. The cys-diabody format enables site-specific radiolabeling and rapid renal clearance, which results in high-contrast images at early time points.</p><p><strong>Procedures: </strong>In this work, an anti-CD4 cys-diabody based on the hybridoma GK1.5 was reengineered by CDR-grafting (GK1.5 FR cDb) for higher expression in mammalian cell lines. An N-glycosylation motif in the variable light chain domain framework was removed by site-directed mutagenesis, resulting in GK1.5 N80D cDb. To investigate the impact of the variable domain glycan on the in vivo biodistribution and pharmacokinetics, both cys-diabodies were site-specifically conjugated with deferoxamine-maleimide and radiolabeled by chelation of zirconium-89. Serial immunoPET/CT imaging was used for non-invasive, whole-body assessment of specific targeting, biodistribution, and differential clearance of the two novel anti-CD4 cys-diabodies.</p><p><strong>Results: </strong>The anti-CD4 cys diabody was successfully re-engineered by CDR-grafting (GK1.5 FR cDb) and aglycosylation (GK1.5 N80D cDb), resulting in a higher expression yield (~ tenfold increase) without impacting antigen specificity or affinity. Both cys-diabody variants were successfully ⁸⁹Zr-radiolabeled with similar specific activity and radiochemical purity. ImmunoPET imaging of ⁸⁹Zr-GK1.5 FR cDb and ⁸⁹Zr-GK1.5 N80D cDb in immunocompetent mice showed CD4 antigen-specific lymphoid tissue uptake in vivo. ⁸⁹Zr-GK1.5 FR cDb exhibited rapid hepatic clearance, resulting in significantly reduced uptake in lymph nodes and the spleen. Removal of the N-glycosylation motif in ⁸⁹Zr-GK1.5 N80D cDb restored diabody-typical biodistribution (renal clearance), resulting in higher target tissue uptake.</p><p><strong>Conclusion: </strong>The novel reengineered anti-CD4 GK1.5 N80D cDb overcomes the previous production yield bottleneck and provides same-day ⁸⁹Zr-immunoPET imaging for non-invasive, whole-body visualization of murine CD4⁺ T cells.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799662","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":"Enhancing the Half-Life of ODAP-Urea Based Radioligands by Incorporating Albumin-Binding Moieties.","authors":"Xiang-Yi Chen, Yan Zhang, Xiaojiang Duan, Jingming Zhang, Zhuochen Zhang, Xing Yang, Zhi-Xiao Wei, Zuo-Xiang He","doi":"10.1007/s11307-025-02035-y","DOIUrl":"https://doi.org/10.1007/s11307-025-02035-y","url":null,"abstract":"<p><strong>Purpose: </strong>Prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT) is a promising approach to treating metastatic castration-resistant prostate cancer (mCRPC). With the emergence of oxalyldiaminopropionic acid urea (ODAP-Urea) based radioligands targeting PSMA, novel paradigms focused on PSMA-RLT are garnering attention. This study aims to assess potentially novel ODAP-Urea-based radioligands prepared for PSMA-RLT.</p><p><strong>Methods: </strong>Albumin binding moieties (ABMs) were selected for optimization. Candidates were evaluated in vitro and subsequently investigated through biodistribution and imaging studies in 22Rv1 tumor-bearing mice.</p><p><strong>Results: </strong>We synthesized five novel ODAP-Urea-based derivatives (CXY-18, CXY-19, CXY-20, CXY-21, CXY-23) with specific ABM. All compounds demonstrated high affinities for PSMA (K_i values ranging from 0.21 nM to 3.6 nM) and strong human albumin protein binding abilities (83.4 ± 1.6% to 94.6 ± 0.4%). [⁶⁸Ga]Ga-CXY-18 (CXY-18) PET/CT exhibited the highest tumor uptake and blood retention properties. Moreover, the internalization of [⁶⁸Ga]Ga-CXY-18 in the 22Rv1 cell line (23.81 ± 1.67%) exceeded that of [⁶⁸Ga]Ga-PSMA-617 (9.99 ± 0.98%). Biodistribution studies confirmed prolonged blood retention and enhanced tumor uptake with [¹⁷⁷Lu]Lu-CXY-18, peaking at 48 h post-injection (4 h: 27.22 ± 3.61%ID/g; 24 h: 30.61 ± 4.96%ID/g; 48 h: 33.92 ± 2.98%ID/g; 96 h: 30.97 ± 1.87%ID/g; 192 h: 9.03 ± 3.49%ID/g).</p><p><strong>Conclusion: </strong>Our study indicates that CXY-18 possesses high PSMA specificity and tumor uptake, underscoring its promising potential for PSMA-RLT using 4-IBA.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799661","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 Study of S1PR1 Expression in Rodent Model of Myocardial Infarction.","authors":"Hong Chen, Lin Qiu, Hao Jiang, Wenjuan Zhou, Anil Kumar Soda, Attila Kovacs, Carla J Weinheimer, Robert J Gropler, Zhude Tu","doi":"10.1007/s11307-025-02039-8","DOIUrl":"10.1007/s11307-025-02039-8","url":null,"abstract":"<p><strong>Purpose: </strong>Acute myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator influencing numerous physiological processes. S1PR1 is the predominant isoform of the S1P receptor in cardiomyocytes and vascular endothelial cells. S1PR1 plays a critical role in preventing adverse cardiac remodeling. The importance of S1PR1 in cardiac physiology has led to the development of novel treatments for MI, including S1PR1 gene delivery strategies aimed at preventing heart failure. Monitoring the dynamic changes of S1PR1 post-MI is clinically significant for assessing cardiac remodeling. This study validated the ability of specific S1PR1 PET radiotracer [¹⁸F]FS1P1 to track changes in this signaling pathway, thereby providing a non-invasive diagnostic tool to quantify S1PR1 expression for investigating MI in vivo.</p><p><strong>Procedures: </strong>We characterized the S1PR1 radiotracer [¹⁸F]FS1P1 in an echo-guided mouse model of MI. [¹⁸F]FDG PET was used to delineate the infarct area. Masson trichrome staining was used to identify cardiac fibrosis. Immunofluorescence (IF) experiment was conducted to demonstrate changes in S1PR1 expression after MI. Autoradiography was performed to evaluate the distribution of [¹⁸F]FS1P1 in MI heart tissues. MI (n = 4) and sham (n = 4) mice were scanned with [¹⁸F]FS1P1 PET at 2 days and 2 weeks post-MI, radioactivity uptake in the myocardium was calculated as the percentage of the injected dose per gram (%ID/g).</p><p><strong>Results: </strong>The uptake of [¹⁸F]FS1P1 was significantly decreased by 31.8% in the infarct region at 2 days post-MI compared to the sham group (1.3 ± 0.3 vs. 1.9 ± 0.3), and decreased by 37.6% at 2 weeks post-MI (1.2 ± 0.5). Additionally, [¹⁸F]FS1P1 signal decreased by 20.8% in the non-infarct remote area at 2 weeks post-MI compared with the sham control (1.6 ± 0.4 vs. 2.0 ± 0.2). Autoradiography study confirmed the trend of decreased [¹⁸F]FS1P1 uptake in the MI tissues. IF studies confirmed that the change in the [¹⁸F]FS1P1 PET signal corresponded with the change in S1PR1 expression.</p><p><strong>Conclusions: </strong>This study demonstrated the downregulation of S1PR1 expression following MI and validated the use of [¹⁸F]FS1P1 PET imaging as an effective tool for detecting changes in S1PR1 expression post-MI.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794906","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":"In vivo Multimodal Magnetic Particle Imaging for Early Detection of Ischemic Stroke in Tree Shrews.","authors":"Bo Zhang, Tao Zhu, Haoran Zhang, Xiaomei Yu, Jie He, Sijia Liu, Yanjun Liu, Zechen Wei, Chaoen Hu, Yali Zhang, Hongdi Huang, Minghao Qiu, Rui Jin, Hongli Li, Huiheng Xie, Jianhong Wang, Hui Hui, Jie Tian","doi":"10.1007/s11307-025-02031-2","DOIUrl":"https://doi.org/10.1007/s11307-025-02031-2","url":null,"abstract":"<p><strong>Purpose: </strong>Ischemic stroke is a significant threat to human life and health, and timely diagnosis is essential for improving patient outcomes. Magnetic Particle Imaging (MPI), as an emerging high-sensitivity imaging technology, holds significant potential for the diagnosis of ischemic stroke. It is necessary to conduct multimodal MPI research based on the characteristics of the animal model and the detection needs of ischemic stroke.</p><p><strong>Procedures: </strong>We used tree shrews, which have a close phylogenetic relationship with primates, as experimental subjects and established a photothrombotic (PT) stroke model. Considering the body size of tree shrews and the high-sensitivity detection requirements for ischemic stroke, a dedicated MPI receiving system for tree shrews was developed based on the primate brain MPI equipment. After validating the MPI system's performance, multimodal MPI fusion imaging of the tree shrew brain was performed by combining magnetic resonance imaging (MRI) and computed tomography (CT).</p><p><strong>Results: </strong>The sensitivity of the receiving system for tree shrews is 0.017 mg Fe/mL, which is 8 times higher than that of the original system. Within one hour after the establishment of the PT stroke model, the MPI signal intensity in ischemic stroke tree shrews was approximately 25% lower than in the control group, while MRI showed no significant differences. On the 6th and 12th days after ischemic stroke onset, MRI images revealed clear lesion locations. Anatomical results of the tree shrew brain revealed significant lesions, confirming the successful establishment of the PT stroke model.</p><p><strong>Conclusions: </strong>The dedicated MPI receiving system developed in this study significantly enhanced MPI sensitivity. The multimodal MPI imaging platform integrates the advantages of MRI and CT structural imaging based on high-sensitivity detection, enabling early detection of ischemic stroke in tree shrews.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794905","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":"Poor Diagnostic Performance of the Melanin-Binding Tracer [18 F]MEL050 in Human Melanoma Indicates Biological Heterogeneity.","authors":"Robert E Ware, Damien Kee, Peter Roselt, Ivan Greguric, Andrew Katsifis, Thomas Bourdier, Wayne Noonan, William Murray, Catherine Mitchell, Marnie Downes, Mark Shackleton, Grant A McArthur, Rodney J Hicks","doi":"10.1007/s11307-025-02025-0","DOIUrl":"10.1007/s11307-025-02025-0","url":null,"abstract":"<p><strong>Purpose: </strong>Malignant melanoma is a highly lethal malignancy typically characterized by the expression of melanin, which is an attractive diagnostic and therapeutic target in these cancers because it is expressed in few other tissues. Following preclinical evaluation of the melanin-targeting PET tracer, [18F]-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide ([18F]MEL050), we sought to evaluate this agent in patients with melanoma.</p><p><strong>Method: </strong>A phase I clinical trial was performed in ten patients with metastatic melanoma. Safety, dosimetry and diagnostic performance of intravenously administered][18F]MEL050 were evaluated. Based on results from this trial, we further assessed the prevalence and prognostic significance of loss of melanin expression in two historical patient cohorts for which there were matching histological and clinical outcome data.</p><p><strong>Results: </strong>Across the trial cohort, no adverse safety signals resulted from [18F]MEL050 administration. The whole-body effective dose was 0.0163 mSV/MBq for an adult male and 0.0206 mSV/MBq for an adult female. The human biodistribution was favorable with low uptake in organs at high risk of metastatic spread, including the brain. Of metastatic sites identified as melanoma on [18F]FDG PET/CT, only 31/65 (48%) were positive on [18F]MEL050 PET. Four [18F]FDG+[18F]MEL050+ metastases were resected from three patients and found to be melanotic by histological examination, whereas five [18F]FDG+[18F]MEL050- metastases from two patients were amelanotic. In our historical cohorts, amelanosis was more common in metastatic than primary disease (45% versus 20%) and the presence of melanin within sentinel lymph node metastases was associated with worse disease-free (HR 2.3 95% CI 1.3 - 4.3, p = 0.002) and disease-specific survivals (HR 3.6, 95% CI 1.4 - 9.7,p = 0.009) in stage III disease, compared with amelanotic sentinel lymph node metastases.</p><p><strong>Conclusion: </strong>We propose caution in the use of melanin-targeted agents for melanoma diagnosis and therapy until their utility as prognostic or predictive imaging biomarkers, and the biological implications of loss of melanin deposition during melanoma progression, are better understood.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"649-657"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}