Imaging of 99Tcm-labeled new cyclic RGDfK Dimer in nude mice bearing U87MG human glioma xenografts
10.3760/cma.j.issn.0253-9780.2010.03.016
- VernacularTitle:99Tcm标记新型RGD环肽在神经胶质瘤动物模型的实验研究
- Author:
Xiao-na, JIN
;
Ji-yun, SHI
;
Yan, LIU
;
Zhao-hui, ZHU
;
Bing, JIA
;
Zhao-fei, LIU
;
Xi-min, SHI
;
Fan, WANG
;
Fang, LI
- Publication Type:Journal Article
- Keywords:
Peptids,cyclic;
Technetium;
Integrin alpha v beta 3;
Glioma;
Radionuclide imaging;
Mice,nude
- From:Chinese Journal of Nuclear Medicine
2010;30(3):195-200
- CountryChina
- Language:Chinese
-
Abstract:
Objective (1) To evaluate the effect of insertion of two 15-amino-4,7,10,13-tetraoxapentadecanoic (2 PEG4 ) linkers into cyclic Arg-Gly-Asp (RGD) Dimer E [c(RGDfK)]2 on receptor binding in vitro, (2) to assess its biodistribution in vivo and (3) to investigate the value of 99Tcm labeled 2PEG4-Dimer for integrin αvβ3-positive tumors imaging.Methods The expression of U87 human glioma cells and integrin αv β3 was determined by immunofluorescence staining.The half-inhibition concentrations (IC50) for 125 I-cyclo (Arg-Gly-Asp-D-Tyr-Lys) (c(RGDyK) ) of c ( RGDyK ), hydrazinonictinamide ( HYNIC )-Dimer and HYNIC-2PEG4-Dimer binding to integrin αvβ3 were measured.99Tcm-HYNIC-Dimer and 99Tcm-HYNIC-2PEG4-Dimer were synthesized using non-SnCl2 formulation.Biodistribution and imaging studies were performed in nude mice bearing human glioma xenografts.The unpaired t test was used for statistical analysis.Results The labeling yield of the two radiotracers was more than 95%, and the radiochemical purity was more than 99% through Sep-Pek C18 cartridge.HYNIC-2PEG4-Dimer had significantly higher binding affinity of integrin αvβ3 than c(RGDyK) and HYNIC-Dimer (IC50 = 0.8 nmol/L, 27 nmol/L and 2.4 nmol/L, respectively).Biodistribution study showed that 99Tcm-HYNIC-2PEG4-Dimer was mainly excreted via the kidney.The tumor uptake of 99Tcm-HYNIC-2PEG4-Dimer was higher than that of 99Tcm-HYNIC-Dimer at 2h post injection ((5.71 ±0.96) and (2.10 ±0.50) % ID/g, t =4.80, P＜0.05).The xenografted tumors were visible at 0.5 h post injection and the image contrast increased with time due to the tracer clearance of the background tissue.Conclusion 99 Tcm-HYNIC-2PEG4-Dimer is a promising radiotracer for integrin αvβ3-positive tumor imaging.
