دورية أكاديمية
From netrin‐1‐targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors
| العنوان: | From netrin‐1‐targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors |
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| المؤلفون: | David Kryza, Jennifer Wischhusen, Mathieu Richaud, Maëva Hervieu, Jacqueline Sidi Boumedine, Jean‐Guy Delcros, Sophie Besse, Thomas Baudier, Pierre‐Alexandre Laval, Silvia Breusa, Erwan Boutault, Hugo Clermidy, Nicolas Rama, Benjamin Ducarouge, Mojgan Devouassoux‐Shisheboran, Jean‐Michel Chezal, Anne‐Laure Giraudet, Thomas Walter, Patrick Mehlen, David Sarrut, Benjamin Gibert |
| المصدر: | EMBO Molecular Medicine, Vol 15, Iss 4, Pp n/a-n/a (2023) |
| بيانات النشر: | Springer Nature, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | cancer, extracellular matrix, netrin, radioimmunotherapy, targeted therapy, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Targeted 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, we report the embryonic navigation cue netrin‐1 as an unanticipated target for vectorized radiotherapy. While netrin‐1, known to be re‐expressed 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. NP137‐111In provided specific detection of netrin‐1‐positive tumors with an excellent signal‐to‐noise ratio using SPECT/CT imaging in different mouse models. The high specificity and strong affinity of NP137 paved the way for the generation of lutetium‐177‐DOTA‐NP137, 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 NP137‐111In and NP137‐177Lu may represent original and unexplored imaging and therapeutic tools against advanced solid cancers. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 20221673 |
| العلاقة: | https://doaj.org/toc/1757-4676Test; https://doaj.org/toc/1757-4684Test |
| DOI: | 10.15252/emmm.202216732 |
| الوصول الحر: | https://doaj.org/article/d9f5252ceab344fca27e6ed88f83c690Test |
| رقم الانضمام: | edsdoj.9f5252ceab344fca27e6ed88f83c690 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 20221673 |
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| DOI: | 10.15252/emmm.202216732 |