99Tcm-AE105的制备及荷胰腺癌裸鼠显像研究  

Synthesis of 99Tcm-HYNIC-AE105 and its application for imaging urokinase plasminogen activator receptors in human pancreatic cancer xenografts by gamma imaging

作　　者：孙芳芳[1] 冯洪波[1] 杨春[1] 张欣[1] 宫晓艳[1] 王光宇[1] 李迪[1] 朱毅[1] 郑红娜[1] 

机构地区：[1]116011,大连医科大学附属第一医院核医学科

出　　处：《中华核医学与分子影像杂志》2013年第6期-,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金

摘　　要：目的 以99Tcm标记尿激酶型纤维蛋白酶原激活剂受体(uPAR)靶向多肽分子D-Cha-F-s-r-Y-L-W-S (AE105),探讨标记产物作为显像剂无创性评价肿瘤组织内uPAR表达的可行性.方法 采用三(羟甲基)甲基甘氨酸(Tricine)作为协同配体,SnCl2为还原剂,应用99Tcm标记AE105及阴性对照多肽D-Cha-F-s-r-Y-L-E-S(AE105mut).采用完全随机法将荷胰腺癌(bxpc-3细胞株)裸鼠模型分为2组,每组30只,分别注射18.5 MBq (0.2 ml)99Tcm-AE105与99Tcm-AE105mt,比较两者体内分布及γ显像结果.采用免疫组织化学方法检测肿瘤组织内uPAR表达,并探讨其与标记物摄取的相关性.数据分析采用两样本t检验和Pearson直线相关分析.结果 99Tcm-AE105标记率达(94.64±0.72)％,放化纯达(97.72±1.73)％,且体外稳定性良好.注射99Tcm-AE105后2h,荷瘤鼠肿瘤显影,4、6h显影清晰;注射99Tcm-AE105mut组始终未见清晰显影.肿瘤组织中99Tcm-AE105的分布均明显高于99Tcm-AE105mut,注射后4h放射性摄取分别为(3.12±0.27) ％ID/g和(1.65±0.53) ％ID/g(t=4.496,P＜0.01);注射后6h放射性摄取分别为(2.98±0.15) ％ID/g和(1.41±0.38)％ID/g(t=6.787,P＜0.01).4～6h肿瘤组织内uPAR表达与99Tcm-AE105摄取呈正相关(r=0.791,P＜0.01),而99Tcm-AE105mut组两者之间无相关性(r=-0.415,P＞0.05).结论 99Tcm-AE105的标记过程简单易行,标记率高,稳定性好,具有良好的uPAR靶向性与特异性,有望应用于临床.Objective To synthesize 99Tcm-labeled urokinase plasminogen activator receptor (uPAR)-binding peptide D-Cha-F-s-r-Y-L-W-S (AE105) (99Tcm-AE105),and evaluate its value as an uPAR imaging agent in pancreatic cancer xenograft models.Methods 99Tcm-AE105 and 99Tcm-D-cha-F-s-r-Y-L-E-S (AE105mut) were synthesized by using Tricine as the coligand and SnC12 as the reductant.Gamma imaging was performed on 2 groups of pancreatic cancer (bxpc-3 cells) xenograft mice models (30 mice in each group,by completely randomized design) post injection of 18.5 MBq (0.2 ml) 99Tcm-AE105 and 99TcmAE10Smut,respectively.The tumor uptake (％ID/g) of the 2 groups was calculated and compared by twosample t test.The uPAR expression was measured by immunohistochemistry.Correlation between uPAR expression and tumor uptake was analyzed by Pearson correlation analysis.Results The labeling efficiency of 99Tcm-AE105 was (94.64±0.72) ％.The radiochemical purity was (97.72± 1.73) ％ after purification and the stability was acceptable.The tumor could be visualized on gamma imaging at 2 h post injection,and better visualized at 4 h and 6 h in the 99Tcm-AE105 group.However,the tumor could not be visualized on garmna imaging in the 99Tcm-AE105mut group.The tumor uptake of 99Tcm-AE105 was higher than that of 99TcmAE105mut(4 h:(3.12±0.27) vs (1.65±0.53) ％ID/g,6 h:(2.98±0.15) vs (1.41±0.38) ％ID/g; t=4.496,6.787,both P＜0.01).Significant correlation between tumor uptake of 99Tcm-AE105 and uPAR expression was found in 4-6 h (r =0.791,P＜0.01).There was no correlation between 99Tcm-AE 105mut uptake and uPAR expression in 4-6 h (r=-0.415,P＞0.05).Conclusion 99Tcm-AE105 could be synthesized with high radiochemical purity.The specific tumor uptake of 99Tcm-AE105,which correlates with uPAR expression in pancreatic cancer,makes it a potential clinical gamma imaging tracer for cancer detection and therapy monitoring.

关 键 词：胰腺肿瘤 受体 尿激酶 同位素标记 锝 放射性核素显像 小鼠 裸 

分 类 号：R817-33[医药卫生—影像医学与核医学]