^(99)Tc^m-ASON的制备及其生物分布

Preparation and Biodistribution of ^(99)Tc^m-ASON

合成了 NHS- MAG3 ,使其与 c- myc m RNA互补的 15个碱基的 5’末端氨基修饰的反义寡核苷酸 (ASON)偶联 ,然后进行 99Tcm标记 ,通过 Sephadex G2 5(φ0 .5cm× 30 cm)分离纯化 99Tcm- ASON,评价其稳定性。结果显示平均标记率为 6 8.4 % ,纯化后 99Tcm- ASON在室温 4 h内放化纯度大于94 % ;与人血清孵育后 ,放化纯度无明显降低 ,与血清蛋白结合较少。荷瘤 BALB/ c裸鼠体内分布研究显示 2 h时肿瘤摄取 99Tcm- ASON达最高值 (6 .2 2 % ID/ g)。以 NHS- MAG3 为螯合剂得到的 99Tcm-ASON具有良好的稳定性 ,在肿瘤部位高浓聚 。

NHS-MAG 3 is synthesized. A 15-base single-stranded amine-derivitized antisense oligonucleotide(ASON) complementary to c-myc oncogene mRNA is coupled with NHS-MAG 3 and labeled with 99 Tc m. 99 Tc m-ASON is purified on a φ 0.5 cm×30 cm gel filtration column of Sephadex G25, then the stability is evaluated. The results show that the average labeling efficiency of 99 Tc m-ASON is 68.4%,the radiochemical purity remained higher than 94% for 4 h after labeling at room temperature. When incubated with fresh human serum, 99 Tc m-ASON is stable, no degeneration is observed and the serum protein binding of 99 Tc m-ASON is low. The biodistribution in tumor-bearing nude mice shows that the highest uptake of tumor is 6.22 %ID/g at 2 h. Using NHS-MAG 3 as an efficient chelator, ASON has been successfully labeled with 99 Tc m. 99 Tc m-ASON has desirable stability, higher uptake in tumor and may provide a new sensitive tool for diagnostic imaging and therapy of tumor in the future.