^(99m)Tc-PDGFR-β AODN的制备及其生物分布

Preparation and biodistribution of ^(99m)Tc-PDGFR-β AODN

目的 :寻求一种理想的99mTc标记大鼠血小板衍化生长因子受体 β(PDGFR β)反义脱氧寡核苷酸 (AODN)的方法 ,并观察标记产物的生物学分布以探讨其用于防治冠状动脉再狭窄的可能性 .方法 :先使长度为 18个碱基的单链PDGFR βAODN与双功能螯合剂NHS MAG3 耦联 ,然后进行99mTc标记 ,测定不同条件下标记率 ,分析确定最佳标记条件 .常规测定放化纯度和比活度 ,并对标记物进行稳定性和正常小鼠体内分布实验 .结果 :①最佳标记条件下平均标记率达 70 %(最高为 73 2 % ) ,经P4层析柱纯化后放化纯度 >95 % ,比活度 7 4～ 11 1MBq(2 0 0～ 30 0 μCi) / μg ;② 99mTc MAG3 AODN在室温下生理盐水中及 37℃下新鲜人血清中稳定性良好 ,与血清蛋白结合率为 6 %～ 8% ;③ 99mTc MAG3 AODN在正常小鼠体内稳定性良好 ,在肾、肝中摄取较高 .结论 :以NHS MAG3 为鳌合剂标记得到的99mTc MAG3 AODN具有良好的稳定性 ,为下一步进行细胞和动物实验提供了基础 .

AIM: To explore a better method of radiolabeling platelet derived growth factor receptor-β(PDGFR-β) antisense oligodeoxynucleotide (AODN) with 99mTc and to investigate the biodistribution of radiolabeled AODN in mice. METHODS: A 18mer single-chain AODN, complementary to PDGFR-β mRNA, was conjugated with chelator NHS-MAG 3 and labeled with 99mTc. The stability of 99mTc-MAG 3-AODN in vitro was investigated and biodistribution was studied in normal mice. The labeling efficiency was measured by paper chromatography. RESULTS: As proved by paper chromatography and P4 column analysis, AODN was successfully radiolabeled by 99mTc. The results showed that the average labeling efficiency reached 70%. In saline at room temperature and in serum at 37℃, the radiochemical purity of 99mTc-MAG 3-AODN was higher than 90% in 24 hours. The biodistribution study in normal mice showed that there was a higher uptake in kidney and liver. CONCLUSION: It is concluded that these strategies for labeling AODN with 99mTc are simple and efficient. 99mTc-MAG 3-AODN is stable in vitro and appears to be suitable for further experiments and therapeutic applications in the future.