Tumor Uptake of the RGD Dimeric Probe 99mTc-G3-2P4-RGD2 is Correlated with Integrin αvβ3 Expressed on both Tumor Cells and Neovasculature

Integrin alpha(v)beta(3) has been well-documented as one of the key players in the process of tumor angiogenesis. Radiolabeled RGD (Arg-Gly-Asp) peptides (flat specifically target integrin alpha(v)beta(3) have Potential for tumor early detection and noninvasively monitoring the status Of tumor angiogenesis. We developed a cyclic RGD dimeric probe Tc-99m-HYNIC-Gly(3)-E[PGDfK)](2) (Tc-99m-G(3)-2P(4)-RGD2) (using tricine and TPPTS as the coligands, TPPTS = trisodium triphenylphosphine-3,3',3 ''-trisulfonate and investigated whether it could be used to noninvasively visualize and quantify integrin alpha(v)beta(3) expression in vivo. HYNIC-Gly(3)-E[PEG(4)-c(RGDfK)](2) was synthesized and labeled with Tc-99m. The biodistribution and planar gamma-imaging studies of Tc-99m-G(3)-2P(4)-RGD2 were performed ill both U87MG (human integrin alpha(v)beta(3) Positive/murine integrin alpha(v)beta(3) positive) and HT-29 (human integrin alpha(v)beta(3) negligible /murine integrin alpha(v)beta(3) positive) tumor-bearing nude mouse models. The correlation of Tc-99m-G(3)-2P(4)-RGD2 tumor uptake values (measured by ex vivo biodistribution) with expression levels Of human integrin alpha(v)beta(3) or murine integrin alpha(v)beta(3) (measured by Western blot) were determined in U87MG and HT-29 tumor models, respectively. Tc-99m-G(3)-2P(4)-RGD2 exhibited increased receptor binding affinity and ill vivo tumor uptake as compared with previously reported RGD dimeric tracer Tc-99m-RGD2 (Without Gly(3) and PEG(4) spacers). The tumor uptake of Tc-99m-G(3)-2P(4)-RGD2 wits related to the expression levels of both human integrin alpha(v)beta(3) (expressed on compared cells) and murine integrin alpha(v)beta(3) (expressed on newborn tumor vasculature). Our results demonstrate that. Tc-99m-G(3)-2P(4)-RGD2 is a useful agent for integrin alpha(v)beta(3) imaging. The relationship between Tc-99m-G(3)-2P(4)-RGD2 uptake and integrin alpha(v)beta(3) expression level its determined by this study would provide useful information for clinical translation of RGD probes.