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
{"title":"通过在甲基纤维素制剂中局部应用EMI-137增强结直肠肿瘤的可视化：一项离体可行性研究。","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":null,"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":2.5000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"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\":null,\"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\":2.5000,\"publicationDate\":\"2025-08-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Imaging and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11307-025-02042-z\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Imaging and Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11307-025-02042-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Enhanced Visualisation of Colorectal Tumours via Topical Application of EMI-137 in a Methylcellulose-Based Formulation: An ex vivo Feasibility Study.
Background: 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.
Methods: 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.
Results: 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.
Conclusion: EMI-137 in a novel viscous vehicle effectively imaged c-Met expressing colon tumors, potentially facilitating fluorescent-guided tumor imaging.
期刊介绍：
Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures.
Some areas that are covered are:
Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes.
The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets.
Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display.
Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging.
Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics.
Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations.
Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.
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