<it>In vivo </it>optical imaging of integrin α V -β 3 in mice using multivalent or monovalent cRGD targeting vectors

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 α V β 3 -positive or negative tumors. Results We chose the human embryonic kidney cells HEK293(β 3 ) (high levels of α V β 3 ) or HEK293(β 1 ) (α V β 3 -negative but expressing α V 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(β 3 ) than in the HEK293(β 1 ) 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 α V β 3 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(β 3 ) and HEK293(β 1 ) tumors, provided tumor/skin ratio above 15. Such an important contrast plus the opportunity to use the HEK293(β 1 ) 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.

Abstract licence: CC BY-NC-ND

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