| Cui Can,Wang Feng,Shao Guoqiang,Luo Liangsheng,Wang Zizheng.Study of microSPECT-CT imaging of mice orthotopic glioma with 99Tcm-Galacto-RGD2[J].Chinese Journal of Radiological Medicine and Protection,2015,35(12):881-885,952 |
| Study of microSPECT-CT imaging of mice orthotopic glioma with 99Tcm-Galacto-RGD2 |
| Received:May 15, 2015 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.12.001 |
| KeyWords:Glioma Target region Molecular imaging Integrin αⅤβ3 Arg-Gly-Asp peptide |
| FundProject:江苏省自然科学基金(SBK20134281);南京市医学科技发展资金(QRX11253) |
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| Abstract:: |
| Objective To investigate the synthesis, in vivo biodistribution of 99Tcm-HYNIC-PEG4-E[PEG4-c(RGDfk)]2(99Tcm-Galacto-RGD2), and its potential usage for targeted imaging of mice orthotopic glioma. Methods 99Tcm-Galacto-RGD2 was synthesized straightforward and its radiochemical purity and stability and distribution in mice were analyzed. MicroSPECT-CT imaging was done in a mice orthotopic glioma model, which had been set up with U87MG cells, after administration of 99Tcm-Galacto-RGD2. Region of interest (ROI) of glioma was drawn on SPECT-CT section images to quantify tumor uptake (%ID/cm3). Glioma was harvested for pathological examination. Linear-regression was used to analyze the relationship between integrin αⅤ β3 and tumor uptake(%ID/cm3). Results The radiochemical purity of 99Tcm-Galacto-RGD2 was (97.7±0.8)% and stable in vitro. Hynic-Galacto-RGD\-2 could specifically bind to integrin αⅤβ3 of tumor cells with a IC50 of (18±3)nmol/L. After tail vein injection, 99Tcm-Galacto-RGD2 was rapidly discharged from the blood, liver, kidneys and had a relative low concentration in normal brain tissue. MicroSPECT-CT imaging demonstrated that, after 60 min of injection, this drug was well uptaken by glioma tumor than that after 30 min (t=7.13,P<0.05), and the tumor to normal brain tissue (T/B) uptake ratio of 99Tcm-Galacto-RGD2 was 13.92±3.43. Injection of HYNIC-Galacto-RGD2 2 min prior to 99Tcm-Galacto-RGD2 injection extensively reduced the uptake of radioactive drug in tumor tissue(t=11.36, P<0.05). Bland-Altman analysis showed that tumor volume based on SPECT-CT imaging measurement had almost same value with the tumor reference volume (95%CI=-11.94%-11.92%). In addition, the tumor uptake of 99Tcm-Galacto-RGD2 and cellular integrin αⅤβ3 expression level had a linear relationship (R2=0.896). Conclusions Stable 99Tcm-Galacto-RGD2 can be synthesized easily and is applicable for microSPECT-CT imaging analysis of orthotopic glioma in mice together with the evaluation of integrin αⅤβ3 level in tumor. |
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