^(99)Tc^m标记右旋糖苷衍生物的制备及其生物分布

Preparation and Biodistribution Study of ^(99)Tc^m Labelled Dextran Conjugates

采用Isolink药盒制备了羰基锝[99 Tcm(CO)3(H2O)3]+,用制备的羰基锝标记右旋糖苷衍生物;将标记物由小鼠的后足脚垫皮下注射,分别于给药后1、4h处死(处死前10min注入专利蓝溶液),取前哨淋巴结(Sentinel Lymph Node,SLN)、次级淋巴结(2LN)、注射点、肝、脾、血,分别测量其放射性计数,计算组织或器官的放射性摄取率,研究甘露糖基和右旋糖苷衍生物相对分子质量对小鼠淋巴结摄取及体内分布的影响。结果显示:当分子中不含甘露糖基时,SLN的摄取率很低,在注射点的摄取也相对较少,并且体内清除较快;而当分子中含有甘露糖基时,SLN的摄取率大幅提高,但在注射点的滞留也显著提高。以上结果表明,分子中的甘露糖基对淋巴结巨噬细胞表面受体具有亲和作用。另外,右旋糖苷衍生物相对分子质量的不同,也会造成不同的生物分布,相对分子质量较大的标记化合物,SLN提取更高,差异显著(P<0.005);此外,标记物的注射剂量和注射体积也会对SLN的摄取产生较大影响。99 Tcm标记的甘露糖基化右旋糖苷衍生物具有优良的淋巴结摄取及体内分布性质,作为潜在的SLN显像剂,值得进一步研究。

99Tcm Mannosylated dextran conjugates were prepared through [99 Tcm, （CO）3]＋ precursor synthesized by carbonyl Isolink kit. The labelled conjugates were injected sub- dermally into the rear loots of the mice, and the patent blue solution was injected at the same site 10 rain before sacrifice. The mice were killed at 1 h and 4 h postinjection, and the samples of different tissues including SLN, 2LN, injection site, liver, spleen, blood were dissected and counted. The uptake in terms was calculated. The results of biodistribution demonstrated that the SLN uptakes of radiopharmaceutical （without mannose in the mole- cules） were rather low and in vivo excretion of these conjugates were comparatively faster, and the uptake of injection site was also low; on the other hand, the SLN uptakes of radio-pharmaceutical （with mannose in their molecules） were much higher than those of their cor- responding dextran conjugates without mannose, but the retention in the injection site of these conjugates increased too. The results indicated that the affinity of mannosyl-dextran conjugates to the receptors on the surface of macrophages in the lymph node. In addition, the different relative molecular mass of dextran conjugates also cause different biodistribu- tion results, the major one had higher SLN uptake, the difference was significant （P〈0. 005） , moreover, the injected dosage of the labelled conjugates also had an affect on SLN uptakes. The [99Tcm（CO）3]＋ labelled mannosylated dextran conjugates showed prom- ising properties as SLN imaging agent and worth further investigation.