Radioiodinated bicyclic RGD peptide for imaging integrin α_vβ₃ in cancers

Integrin α_vβ₃ is an effective marker of angiogenesis in cancer, and α_vβ₃-specific imaging can yield important details about this complex physiological process. We utilized the recently reported and highly α_vβ₃-specific peptide, bicyclic RGD (bcRGD), as the basic structure of an in vivo α_vβ₃ imaging probe, and synthesized a radioiodinated form of bcRGD, namely [¹²⁵I]bcRGD, with high radiochemical purity (>99%) and high molar activity (81 GBq/μmol). As expected, [¹²⁵I]bcRGD exhibited high selectivity for α_vβ₃ compared with α_vβ₅ and α₅β₁in vitro. [¹²⁵I]bcRGD showed significantly higher accumulation in U-87MG cells (1.6% dose/mg) with high expression of α_vβ₃ compared to A549 cells (0.3% dose/mg) with only moderate expression. Furthermore, 30 min after administration to tumor-bearing mice, [¹²⁵I]bcRGD showed significantly higher accumulation in U-87MG tumors (3.8% ID/g) than in A549 tumors (2.1% ID/g), and the radioactivity accumulation ratios of U-87MG tumor/blood and U-87MG tumor/muscle were 4.0 and 6.0, respectively. These results highlight the promising properties of [^123/125I]bcRGD for use as an in vivo α_vβ₃ imaging probe, as well as the utility of bcRGD as a basic structure of molecular probes for both imaging and therapeutic applications. bcRGD may exhibit broad use in future theranostics applications targeting integrin α_vβ₃-related diseases.