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 [99mTc(CO)3(H2O)3]+. 99mTc labeled glucosamino-D-c(RGDfK) ([99mTc]2) was prepared in 90–93% radiochemical yields (decay corrected). In vitro cell binding assays demonstrated selective binding [99mTc]2 to human umbilical vein endothelial (HUVE) cells, with inhibition of binding to 37.3% of control levels by 10 μM of cold authentic compounds. In addition, [99mTc]2 was shown to have high binding affinity to purified αvβ3 integrin (IC50 = 1.5 nM). These results suggest that these radiolabeled RGD glycopeptides may have value for non-invasive assessment of angiogenesis.

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