99Tcm-DTPA-环九肽用于前列腺癌骨转移白细胞介素11受体显像的实验研究  

A novel 99Tcm labelled polypeptide analogue for interleukin-11 receptor imaging in a bone metastases model for prostate cancer

作　　者：吴清华[1] 刘璐[1] 黄庆娟[2] 杨泽萱[1] 孙晋[1] 刘标[2] 

机构地区：[1]东南大学医学院核医学技术研究所,南京210009 [2]江苏省人民医院核医学科

出　　处：《中华核医学杂志》2010年第6期404-409,共6页Chinese Journal of Nuclear Medicine

基　　金：国家自然科学基金（30470500）

摘　　要：目的 建立99Tcm标记白细胞介素11（IL11）类似物环九肽,即环状肽半胱氨酰-甘氨酰-精氨酰-精氨酰-丙氨酰-甘氨酰-甘氨酰-丝氨酰-半胱氨酸[c（CGRRAGGSC）]的方法,探讨标记物用于前列腺癌骨转移IL11受体（IL11R）显像的可行性.方法 采用间接法,用99Tcm标记c（CGRRAGGSC）制备99Tcm-DTPA-环九肽[99Tcm-DTPA-Bz-NH-SA-c（CGRRAGGSC）,简称99Tcm-DTPA-IL11RR].利用纸层析法及高效液相色谱（HPLC）测定标记率和稳定性.将99Tcm-DTPA-IL11RR（0.74 MBq/只）经正常ICR小鼠尾静脉注射后,观察其在小鼠体内生物学分布,计算血、脑、心、肝、脾、肺、肾、胃、小肠、肌肉、甲状腺、骨骼、胰腺每克组织百分注射剂量率（%ID/g）.γ显像动态（5只小鼠）观察99Tcm-DTPA-IL11RR在荷人PC-3前列腺癌骨转移瘤BALB/c裸鼠模型体内0.5,1,2,4,6,8和24 h表现,与99Tcm-亚甲基二膦酸盐（MDP）骨显像比较,采用感兴趣区（ROI）法计算99Tcm-DTPA-IL11RR显像肿瘤/对侧正常骨骼放射性（T/NT）比值,并用此2种显像剂进行裸鼠骨折模型显像比较.进行体内竞争抑制显像（3只荷瘤裸鼠）,观察标记物生物学活性.对计量资料数据行单因素方差分析.结果 99Tcm-DTPA-IL11RR标记率90.7%,HPLC即时测放化纯为（99.57±0.09）%,室温放置1,2,3,4,6,8和24 h,放化纯依序为（99.29±0.18）%,（98.95±0.78）%,（98.67±0.11）%,（96.53±0.91）%,（95.20±0.70）%,（88.38±0.22）%和（36.17±1.29）%.标记物经正常ICR小鼠尾静脉注射后主要经肾排泄,各时相重要组织脏器普遍摄取较低,肌肉和脑最低,4 h骨骼、肝摄取达峰值,分别为（1.910±0.109）和（0.366±0.030）%ID/g.注射后24 h体内放射性消失.模型鼠γ动态显像示脊柱骨髓、四肢关节髓腔轻度显影,体内放射性清除迅速;瘤灶放射性持续摄取,4 h最明显,延续至6～8 h;24 h全身影像极淡.以ROI法测量的模型鼠0.5,1,2,4,6,8和24 h T/NT比值分别为1.17±0.17,2.20±0.29,3.Objective To assess the feasibility of a novel 99Tcm labelled polypeptide analogue for interleukin-11 receptor （ IL11R） imaging in a bone metastases model for prostate cancer. Methods A novel circular polypeptide analogue of IL11 （ c（ CGRRAGGSC ） ） was indirectly labeled with 99Tcm and the product was named as 99Tcm-DTPA-IL11 RR. The labeling efficiency, radiochemical purity and stability of the product were measured with paper chromatography and high performance liquid chromatography （HPLC）. The biodistribution of 99Tcm-DTPA-IL11RR was investigated in 28 ICR normal mice. The organ radioactivity was measured as percentage activity of injection dose per gram of tissue （ %ID/g）. The models of bone metastases from prostate cancer were established at the tibias of BALB/c nude mice bearing human prostate cancer PC-3 cells. The tumor bearing （ n= 5 ） and standard closed fracture nude mice models underwent both 99Tcm-DTPA-IL11RR and 99Tcm-methylene diphosphonate （MDP） scintigraphy study. The images were acquired at 0.5, 1,2, 4, 6, 8, 24 h after intravenous injection of the tracers. The competitive inhibition imaging was perfomed in three tumor bearing mice. One-way variance analysis was used. Results The labeling efficiency was 90.7%. The radiochemical purity of 99Tcm-DTPA-IL11RR in normal saline solution was （99.57 ±0.09）%, （99.29 ±0.18）%, （98.95 ±0.78）%, （98.67 ±0.11）%, （96.53 ±0.91）%, （95.20±0.70）%, （88.38 ±0.22）% and （36.17±1.29）% at room temperature after0, 1,2, 3, 4, 6, 8 and 24 h, respectively. The tracer radiochemical purity in the blood of ICR mice remained over 90% at 37 C for 6 h. The labeling compounds were excreted mainly through kidney. The peak uptake of bone （ （ 1.910 ±0.109） %ID/g） and liver （ （0.366 ±0.030） %ID/g） was at 4 h after injection. In the tumor bearing mice, the uptake of spine marrow and large joints of extremities was mild. The highest uptake at tumor region was at 4 h and persistent at 6-8 h after injecti

关 键 词：肽类 环 锝 受体 白介素11 前列腺肿瘤 肿瘤转移 骨骼 放射性核素显像 小鼠 

分 类 号：R686[医药卫生—骨科学]