Synthesis of Tc-99m labeled glucosamino-Asp-cyclic(Arg-Gly-Asp-d-Phe-Lys) as a potential angiogenesis imaging agent

Angiogenesis imaging agents for single photon emission computed tomography (SPECT) play a role in diagnosing tumor-induced angiogenesis as well as tumor metastasis. We synthesized and evaluated radiolabeled RGD glycopeptides by incorporation of the [(99m)Tc(CO)(3)(H(2)O)(3)](+). (99m)Tc labeled glucosamino-D-c(RGDfK) ([(99m)Tc]2) was prepared in 90-93% radiochemical yields (decay corrected). In vitro cell binding assays demonstrated selective binding [(99m)Tc]2 to human umbilical vein endothelial (HUVE) cells, with inhibition of binding to 37.3% of control levels by 10 microM of cold authentic compounds. In addition, [(99m)Tc]2 was shown to have high binding affinity to purified alpha(v)beta(3) integrin (IC(50)=1.5 nM). These results suggest that these radiolabeled RGD glycopeptides may have value for non-invasive assessment of angiogenesis.