| 崔璨,王峰,邵国强,罗良生,王自正.原位脑胶质瘤99Tcm-Galacto-RGD2 microSPECT/CT靶向显像研究[J].中华放射医学与防护杂志,2015,35(12):881-885,952 |
| 原位脑胶质瘤99Tcm-Galacto-RGD2 microSPECT/CT靶向显像研究 |
| Study of microSPECT-CT imaging of mice orthotopic glioma with 99Tcm-Galacto-RGD2 |
| 投稿时间：2015-05-15 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.12.001 |
| 中文关键词: 脑胶质瘤 靶区 分子显像 整合素αⅤβ3 精氨酸-甘氨酸-天冬氨酸多肽 |
| 英文关键词:Glioma Target region Molecular imaging Integrin αⅤβ3 Arg-Gly-Asp peptide |
| 基金项目:江苏省自然科学基金(SBK20134281);南京市医学科技发展资金(QRX11253) |
|
| 摘要点击次数: 2808 |
| 全文下载次数: 2541 |
| 中文摘要: |
| 目的 合成 99Tcm-半乳糖化精氨酸-甘氨酸-天冬氨酸多肽(99Tcm-HYNIC-Galacto-RGD2-tricine-TPPTS, 99Tcm-Galacto-RGD2),探讨其用于原位胶质瘤靶向显像的价值。方法 一步法制备99Tcm-Galacto-RGD2,考察其体内外稳定性及体内生物学分布;构建荷人原位脑胶质瘤(U87MG)动物模型,99Tcm-Galacto-RGD2尾静脉注射后行microSPECT/CT显像,勾画肿瘤感兴趣区,定量肿瘤的放射性摄取,病理学检查肿瘤整合素αⅤβ3表达水平,与放射性摄取进行相关性分析。结果99Tcm-Galacto-RGD2放射化学纯度为(97.7±0.8)%,体内外稳定性好,能与脑胶质瘤细胞特异性结合,IC50为(18±3)nmol/L。裸鼠尾静脉注射后血液清除快,脑组织放射性摄取少。静脉注射60 min后,肿瘤放射性摄取明显高于30 min(t=7.13, P<0.05),1 h肿瘤/脑组织放射性摄取比为13.92±3.43。microSPECT-CT显像阻断2 min后,肿瘤放射性摄取显著低于非阻断组(t=11.36,P<0.05);基于microSPECT-CT显像勾画肿瘤感兴趣区获得的肿瘤体积与肿瘤参考体积具有较好的一致性(95%CI=-11.94%~11.92%)。肿瘤99Tcm-Galacto-RGD2摄取与整合素αⅤβ3表达水平呈线性相关(R2=0.896)。结论 99Tcm-Galacto-RGD2易于合成,理化性质好,microSPECT-CT融合显像可用于脑胶质瘤病灶的感兴趣区勾画和评价肿瘤组织整合素αⅤβ3的表达水平。 |
| 英文摘要: |
| 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. |
| HTML 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|