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.
Lee
Byung Chul
BC
Department of Chemistry, Inha University, 253 Yonghyundong, Namgu, Inchon 402-751, Republic of Korea.
Sung
Hyun Ju
HJ
Kim
Ji Sun
JS
Jung
Kyung-Ho
KH
Choe
Yearn Seong
YS
Lee
Kyung-Han
KH
Chi
Dae Yoon
DY
D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005944:Glucosamine; D006801:Humans; D020128:Inhibitory Concentration 50; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding; D013667:Technetium
D003287:Contrast Media; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D013667:Technetium; D005944:Glucosamine