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In vivo optical imaging of integrin alphaV-beta3 in mice using multivalent or monovalent cRGD targeting vectors
| Content Provider | Semantic Scholar |
|---|---|
| Author | Jin, Zhao-Hui Josserand, Véronique Foillard, Stéphanie Boturyn, Didier Dumy, Pascal Favrot, M. Jean Coll, Luc |
| Copyright Year | 2018 |
| Abstract | Background: The cRGD peptide is a promising probe for early non-invasive detection of tumors. This study aimed to demonstrate how RAFT-c(-RGDfK-)4, a molecule allowing a tetrameric presentation of cRGD, improved cRGD-targeting potential using in vivo models of αVβ3-positive or negative tumors. Results: We chose the human embryonic kidney cells HEK293(β3) (high levels of αVβ3) or HEK293(β1) (αVβ3-negative but expressing αV and β1) engrafted subcutaneously (s.c.) in mice. Non-invasive in vivo optical imaging demonstrated that as compared to its monomeric cRGD analogue, Cy5-RAFT-c(-RGDfK-)4 injected intravenously had higher uptake, prolonged retention and markedly enhanced contrast in HEK293(β3) than in the HEK293(β1) tumors. Blocking studies further demonstrated the targeting specificity and competitive binding ability of the tetramer. Conclusion: In conclusion, we demonstrated that Cy5-RAFT-c(-RGDfK-)4 was indeed binding to the αVβ3 receptor and with an improved activity as compared to its monomeric analog, confirming the interest of using multivalent ligands. Intravenous injection of Cy5-RAFT-c(-RGDfK-)4 in this novel pair of HEK293(β3) and HEK293(β1) tumors, provided tumor/skin ratio above 15. Such an important contrast plus the opportunity to use the HEK293(β1) negative control cell line are major assets for the community of researchers working on the design and amelioration of RGD-targeted vectors or on RGD-antagonists. Background The tripeptide sequence Arg-Gly-Asp (RGD) [1,2] is a well known motif recognizing and interacting with integrin, a family of transmembrane heterodimeric glycoproteins composed of one α and one β subunits [3,4]. The structure of a cyclic pentapeptide containing RGD was optimized in order to provide a high affinity and selectivity for the αVβ3 integrin [5], an integrin overexpressed at the surPublished: 12 June 2007 Molecular Cancer 2007, 6:41 doi:10.1186/1476-4598-6-41 Received: 28 March 2007 Accepted: 12 June 2007 This article is available from: http://www.molecular-cancer.com/content/6/1/41 © 2007 Jin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Molecular Cancer 2007, 6:41 http://www.molecular-cancer.com/content/6/1/41 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.hal.inserm.fr/inserm-00176674/document |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
