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This study proposes embryonic guidance cue netrin-1 as an unexpected target for vectorized radiotherapy. It shows netrin-1 is poorly diffusible and bound to extracellular matrix, enabling imaging and therapy with NP137. NP137-111 provides SPECT/CT detection of netrin-1-positive tumors with high signal-to-noise, while NP137-177Lu induces antitumor effects and extended survival in mouse models, supporting clinical translation.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/from-netrin-1-targeted-spectct-to-internal-radiotherapy-for-management-of-advanced-solid-tumors/384592/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/from-netrin-1-targeted-spectct-to-internal-radiotherapy-for-management-of-advanced-solid-tumors/384592.png","ImageObject",300,407,{"name":92,"@type":93},"Emma Wilson","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main goal of the study described in the abstract?","Question",{"text":113,"@type":114},"To use netrin-1 as a therapeutic and diagnostic target for advanced solid cancers by developing imaging and targeted radiotherapy agents based on NP137.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How is netrin-1 characterized in this work compared with prior assumptions?",{"text":118,"@type":114},"Although netrin-1 is often treated as a diffusible ligand, the study demonstrates it is poorly diffusible and bound to the extracellular matrix.",{"name":120,"@type":111,"acceptedAnswer":121},"What do NP137-111 and NP137-177Lu contribute in tumor management?",{"text":122,"@type":114},"NP137-111 enables SPECT/CT detection of netrin-1-positive tumors with excellent signal-to-noise ratio, and NP137-177Lu provides systemic therapeutic effects and prolonged survival in mouse models.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},384592,1790874172,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},3848291630094,"https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Article  \nFrom netrin-1-targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors  \nDavid Kryza1, 2,*,†, Jennifer Wischhusen3,†, Mathieu Richaud3,4,†, Ma€eva Hervieu3,4, Jacqueline Sidi Boumedine1,4, Jean-Guy Delcros5 , Sophie Besse6, Thomas Baudier7 ,  \nPierre-Alexandre Laval3, Silvia Breusa1,3,4 , Erwan Boutault6, Hugo Clermidy3 , Nicolas Rama3 , Benjamin Ducarouge8 , Mojgan Devouassoux-Shisheboran9, Jean-Michel Chezal6 ,  \nAnne-Laure Giraudet2, Thomas Walter3,4,10, Patrick Mehlen3,**, David Sarrut7,*** & Benjamin Gibert3,4,****  \nAbstract  \nTargeted radionuclide therapy is a revolutionary tool for the treatment of highly spread metastatic cancers. Most current approaches rely on the use of vectors to deliver radionuclides to tumor cells, targeting membrane-bound cancer-specific moieties. Here, wereport the embryonic navigation cue netrin-1 as an unanticipated target for vectorized radiotherapy. While netrin-1, known to be reexpressed in tumoral cells to promote cancer progression, is usually characterized as a diffusible ligand, we demonstrate here that netrin-1 is actually poorly diffusible and bound to the extracellular matrix. A therapeutic anti-netrin-1 monoclonal antibody (NP137) has been preclinically developed and was tested in various clinical trials showing an excellent safety profile. In order to provide a companion test detecting netrin-1 in solid tumors and allowing the selection of therapy-eligible patients, we used the clinical-grade NP137 agent and developed an indium-111-NODAGA-NP137 single photon emission computed tomography (SPECT) contrast agent. NP137-111 In provided specific detection of netrin-1-positive tumors with an excellent signal-to-noise ratio using SPECT/CT imaging indifferent mouse models. The high specificity and strong affinity of NP137 paved the way for the generation of lutetium-177-DOTA-  \nNP137, a novel vectorized radiotherapy, which specifically accumulated in netrin-1-positive tumors. We demonstrate here, using tumor cell-engrafted mouse models and a genetically engineered mouse model, that a single systemic injection of NP137-177Lu provides important antitumor effects and prolonged mouse survival. Together, these data support the view that NP137-111 In and NP137-177 Lu may represent original and unexplored imaging and therapeutic tools against advanced solid cancers.  \nKeywords cancer; extracellular matrix; netrin; radioimmunotherapy; targeted therapy  \nSubject Categories Cancer; Pharmacology & Drug Discovery  \nDOI 10.15252/emmm.202216732 | Received 6 September 2022 | Revised 8 February 2023 | Accepted 10 February 2023 | Published online 6 March 2023 EMBO Mol Med (2023) 15: e16732  \nIntroduction  \nNetrin-1 is known to be crucial during embryonic development and more particularly in the establishment of the central nervous system, through its role in neuronal navigation as exemplified in  \n1 Imthernat, LAGEPP, CNRS UMR 5007, Universit de Lyon, Hospices Civils de Lyon, Lyon, France  \n2 Lumen Nuclear Medicine group, Hospices Civils de Lyon et Centre Lon Brard, Lyon, France  \n3 Apoptosis, Cancer and Development Laboratory-Equipe labellise ‘ La Ligue’, LabEx DEVweCAN, Institut Convergence PLAsCAN, Centre de Recherche en Cancrologie de Lyon, INSERM U1052-CNRS 5286, Universit de Lyon1, Lyon, France  \n4 Gastroenterology and technologies for health, Centre de Recherche en Cancrologie de Lyon, INSERM U1052-CNRS5286, Universit Lyon 1, Lyon, France  \n5 Small molecules for biological targets, Centre de Recherche en Cancrologie de Lyon. UMR INSERM 1052 – CNRS 5286 ISPB Rockefeller, Lyon, France  \n6 Universit Clermont Auvergne, Inserm, Imagerie Molculaire et Stratgies Thranostiques, Clermont-Ferrand, France  \n7 CREATIS, INSA Lyon, INSERM U1206 – CNRS UMR 5220, Universit de Lyon, Lyon, France  \n8 Netris Pharma, Lyon, France  \n9 Hospices Civils de Lyon, Department of Pathology, Lyon, France  \n10 Hospices Civils de Lyon, H^opital Edouard Herriot, Service de Gastroentrologie et ","cbCailtA9IxzBqv7","https://ap.wps.com/l/cbCailtA9IxzBqv7","pdf",3712595,13,"English","# Abstract\n# Keywords\n# Introduction","[{\"question\":\"What is the main goal of the study described in the abstract?\",\"answer\":\"To use netrin-1 as a therapeutic and diagnostic target for advanced solid cancers by developing imaging and targeted radiotherapy agents based on NP137.\"},{\"question\":\"How is netrin-1 characterized in this work compared with prior assumptions?\",\"answer\":\"Although netrin-1 is often treated as a diffusible ligand, the study demonstrates it is poorly diffusible and bound to the extracellular matrix.\"},{\"question\":\"What do NP137-111 and NP137-177Lu contribute in tumor management?\",\"answer\":\"NP137-111 enables SPECT/CT detection of netrin-1-positive tumors with excellent signal-to-noise ratio, and NP137-177Lu provides systemic therapeutic effects and prolonged survival in mouse models.\"}]","From netrin-1-targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors | PDF",1790264160,33]