钬-166-壳聚糖复合物（DW-166HC）在大鼠和小鼠体内的生物分布及动力学

Biodistribution and kinetics of holmium-166-chitosan complex (DW-166HC) in rats and mice.

作者信息

Suzuki Y S, Momose Y, Higashi N, Shigematsu A, Park K B, Kim Y M, Kim J R, Ryu J M

机构信息

Institute of Whole Body Metabolism, Chiba, Japan.

出版信息

J Nucl Med. 1998 Dec;39(12):2161-6.

PMID:9867162

Abstract

UNLABELLED

The fate of 166Ho-chitosan complex, a radiopharmaceutical drug for cancer therapy, was determined by studying its absorption, distribution and excretion in rats and mice.

METHODS

Holmium-166-chitosan complex [0.75 mg of Ho(NO3)3 x 5H2O and 1 mg chitosan/ head] was administered intrahepatically to male rats. Radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution in tissues were examined. To determine the effects of chitosan in 166Ho-chitosan complex, 166Ho alone [0.75 mg of Ho(NO3)3 x 5H2O/head] was intrahepatically administered to male rats, and radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution were examined. In B16 melanoma-transplanted nude mice, radioactive distribution after intratumoral administration of 166Ho-chitosan complex [0.075 mg of Ho(NO3)3 x 5H2O and 0.10 mg chitosan/head] was investigated also.

RESULTS

After administration of 166Ho-chitosan complex, the radioactive concentrations in blood were low, and cumulative urinary and fecal excretions over a period of 0-72 hr were 0.53% and 0.54%, respectively. The radioactive concentrations in tissues and the whole-body autoradiography images showed that most of the administered radioactivity was localized at the administration site, and only slight radioactivity was detected from the liver, spleen, lungs and bones. On the other hand, results of intrahepatic administration of 166Ho alone showed high radioactive concentrations in the blood, and the whole-body autoradiographs showed that the administered radioactivity was distributed in many organs and tissues. These results strongly suggest that 166Ho is retained at the administration site only when it forms a chelate complex with chitosan. Autoradiographs after intratumoral administration of 166Ho-chitosan complex showed that radioactivity was localized at the site of administration without distribution to the other organs and tissues.

CONCLUSION

Administered 166Ho-chitosan complex is retained at the administration site after either intrahepatic or intratumoral administration to rats or tumor-transplanted nude mice.

摘要

未标记

通过研究166Ho-壳聚糖复合物（一种用于癌症治疗的放射性药物）在大鼠和小鼠体内的吸收、分布和排泄情况，确定了其命运。

方法

将钬-166-壳聚糖复合物[0.75毫克Ho(NO3)3·5H2O和1毫克壳聚糖/只]经肝内注射给雄性大鼠。检测血液中的放射性浓度、尿液和粪便排泄情况以及组织中的放射性分布。为了确定壳聚糖在166Ho-壳聚糖复合物中的作用，将单独的166Ho[0.75毫克Ho(NO3)3·5H2O/只]经肝内注射给雄性大鼠，并检测血液中的放射性浓度、尿液和粪便排泄情况以及放射性分布。在移植了B16黑色素瘤的裸鼠中，还研究了瘤内注射166Ho-壳聚糖复合物[0.075毫克Ho(NO3)3·5H2O和0.10毫克壳聚糖/只]后的放射性分布。

结果

注射166Ho-壳聚糖复合物后，血液中的放射性浓度较低，0至72小时内尿液和粪便累积排泄率分别为0.53%和0.54%。组织中的放射性浓度和全身放射自显影图像显示，大部分注入的放射性物质都集中在注射部位，仅在肝脏、脾脏、肺和骨骼中检测到少量放射性。另一方面，单独经肝内注射166Ho的结果显示血液中的放射性浓度较高，全身放射自显影显示注入的放射性物质分布于许多器官和组织中。这些结果强烈表明，只有当166Ho与壳聚糖形成螯合物时，它才会保留在注射部位。瘤内注射166Ho-壳聚糖复合物后的放射自显影显示，放射性物质集中在注射部位，未分布到其他器官和组织。