Synthesis, in vitro, and in vivo characterization of an integrin αvβ3-targeted molecular probe for optical imaging of tumor

Integrin αvβ3-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy

“…After obtaining the curve fittings by SigmaPlot (Figure 2A), the calculated IC 50 concentration of inhibitors RGDfK and IAC for vitronectin binding to integrin α v β 3 were 4.05 nM and 3.38 nM, respectively. These results confirmed the relatively comparable binding affinities of IAC and RGDfK to integrin α v β 3 protein and closely matched the reported IC 50 of 2.94 ± 0.19 nM for IAC by Burnett et al 27 The lower IC 50 of RGDfK than that noted by Burnett et al for cyclo-(RGDfV) (6.41 ± 0.49 nM) might be due to the different amino acids in the two peptides valine (V) and lysine (K), with the amine group in lysine potentially affording greater protein binding.…”

“…We found that IAC has similar affinity to integrin α v β 3 as RGDfK in the competitive ELISA and the sandwich ELISA and that the difference is not as significant as previous reports. 27 Because of the relatively small difference in the binding affinity to …”

“…In addition to RGD peptides, some research groups have synthesized small molecule antagonists based on RGD motifs to achieve comparable affinity with integrin α v β 3 . [27][28][29] In this study we compared the binding affinities to integrin α v β 3 of the cyclo(RGDfK) (cyclo(Arg-Gly-Asp-D-Phe-Lys)) peptide and the synthesized antagonist 4-[2- (3,4,5,6- Figure 1B) 27 and their NS conjugates by three different (ELISAs). The binding specificity of NSRGDfK to integrin α v β 3 -expressing U87 tumor cells was then validated by silver staining assays.…”

First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with68Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for αvβ3Integrin Receptor Targeting

“…8,9,25 Thus, this novel integrin-targeting platform was expected to have potential applications for targeted delivery of drugs, and more directly, highly suitable for molecular imaging and possibly therapy applications. 26 IAC has been labeled with 99m Tc and 111 In, 9,25 conjugated with a dye, FITC, and evaluated as an optical imaging agent. 19,26 Thus, in vivo studies were performed aimed at rapid targeting of integrin receptors to produce a high tumor-to-background ratio and as well in the cardiovascular setting as an optical imaging agent.…”

Inhibition of integrin αVβ3prevents urokinase plasminogen activator-mediated impairment of cerebrovasodilation after cerebral hypoxia/ischemia

“…The integrin ␣ V ␤ 3 contributes to the attachment of cells to the endothelium (29) and is upregulated in ischemia (30). ␣ V ␤ 3 interacts with the peptide Arg-Gly-aspartic acid (RGD), and binding is inhibited by cyclo(Arg-Gly-Asp-D-PheVal) (cRGDfV) (6). The inhibition of integrin ␣ V ␤ 3 extends the therapeutic window of tissue plasminogen activator (tPA) therapy in a rat stroke model (37).…”