Radiosynthesis and evaluation of 188Re-c(RGDyK)-His as a novel radiotherapeutic agent for integrin αvβ3 targeting tumour
- 137 Downloads
The successes of noninvasive methods to visualize and quantify integrin αvβ3 expression in vivo have paved the way for radiolabeling anti-integrin therapy in clinic. Arginine-glycine-aspartice (RGD) peptide and related derivatives labeled with radionuclides for radio-therapy, which specifically targeting integrin αvβ3-positive tumors, could be used to treat these tumors. We have labeled c(RGDyK)-His, a RGD derivative, with 188Re and the radio-therapy efficiency has been evaluated in model nude mice. c(RGDyK)-His was labeled with 188Re by chelating with [188Re(CO)3(H2O)3]+ under a slightly basic condition. The in vitro specific binding affinity to U87 MG cell lines and the biodistribution of 188Re-c(RGDyK)-His in the animal tumor models was measured. The inhibitory effects of 188Re-c(RGDyK)-His were observed more than 1 month, and evaluated by microPET/CT imaging with 18F-FDG. Results of in vivo, cell uptake demonstrated 188Re-c(RGDyK)-His had a high specific binding affinity to receptor integrin αvβ3. In biodistribution experiment, 188Re-c(RGDyK)-His was accumulated in the tumor and cleared fast from the normal tissues. In radiotherapy study, tumor growth inhibition was significantly higher in the treatment groups than in the control groups. These studies showed that 188Re-c(RGDyK)-His could be effectively used for integrin αvβ3 targeting therapy. This may offer a potential therapeutic strategy for the treatment of integrin-positive tumors in clinic.
Keywords188Re-c(RGDyK)-His Integrin Targeting therapy MicroPET/CT
This work was supported Natural Science Foundation of China under Contract No. 81101066.
- 1.Shiotsu Y (2003) Current screening for molecular target therapy of cancer. Jpn J Cancer Chemother 30:1863–1872Google Scholar
- 4.Niels R, Liu W, Syed AA, Fan F, Oliver S, Oliver S, Oliver S, Alexander AP, Corazon DB, Gary EG, Maureen AN, William FW, Lee ME (2003) αvβ3 integrin antagonist S247 decreases colon cancer metastasis and angiogenesis and improves survival in mice. Cancer Res 63:2079–2087Google Scholar
- 6.Oliver S, Bjarne K, Janette C, Isabelle M, Claudia G, Roland HG, Hans-Jürgen W, Roland H, Gabriele P, Markus H, Hans AK, Horst K, Jörg-Christian T, Markus S, Ambros JB (2009) Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F]Galacto-RGD positron emission tomography. Neuro-Oncol 11:861–870CrossRefGoogle Scholar
- 7.Roland H, Wolfgang AW, Ambros JB, Eugenija V, Daniel R, Mario S, Karl-Friedrich B, Michael G, Rüdiger H, Hans-Jürgen W, Horst K, Markus S (2005) Noninvasive visualization of the activated αvβ3 integrin in cancer patients by positron emission tomography and [18F]galacto-RGD. PloS Med. 2:0244–0252CrossRefGoogle Scholar
- 10.Xilin S, Yongjun Y, Shuanglong L, Qizhen C, Min Y, Nouri Neamati, Baozhong S, Gang N, Xiaoyuan C (2011) 18F-FPPRGD2 and 18F-FDG PET of response to abraxane therapy. J Nucl Med 52:1140–1146Google Scholar