荷瘤鼠膀胱内灌注125^I-UdR的生物学分布及安全性

目的研究125^I-脱氧尿嘧啶核苷（125^I-UdR）在膀胱癌大鼠模型中的分布和安全性,为125^I-UdR的临床应用做准备。方法（1）大鼠膀胱内灌注N-甲基亚硝基脲（MNU）2mg/次,每2周1次,共4次。进行膀胱黏膜病理学动态观察。（2）荷瘤鼠膀胱内灌注相对合适剂量（37.5MBq/kg）的125^I-UdR,通过SPECT显像和γ计数仪测量各脏器放射性活度来了解125^I-UdR在荷瘤鼠体内的分布规律;分析膀胱灌注125^I-UdR后外周血常规、肝肾功能及病理结果,评价125^I-UdR的安全性。结果（1）10周后大鼠膀胱致癌率为100%。（2）荷瘤鼠膀胱灌注125^I-UdR主要分布在膀胱肿瘤及其周围膀胱组织内,肝、脾、肾、肺有少量分布,外周血常规及肝肾功能无明显变化,正常组织无明显病理改变。结论荷瘤鼠膀胱内灌注125^I-UdR（37.5MBq/kg）是安全可行的。

Distribution and Safety After Intravesical Instillation of 5-[~(125)I]iodo-2'- Deoxyuridine in Tumor-bearing Rat

Objective To investigate the distribution and safety of 125^I-UdR in tumor-bearing rat for the preparation of clinic application of 125^I-UdR. Methods （1） A double-weekly dose of 2 mg N -methy1-N-nitrosourea（MNU） was given each time giving 4 times intravesicular administration was given. The pathological dynamic changes of bladder mucosa were observed. （2） A relatively suitable therapeutic dose of intravesical administration of 125^I-UdR was 37.5 MBq/kg in tumor-bearing rat blader. The distribution of 125^I-UdR was estimated by SPECT scintigrams and the radioactivity of various organs determined was analized by γ scintillation counter after intravesical instillation of 125^I -UdR. The pharmic safety of tumor-bearing rats were evaluated by analyzing hemogram,biochemistry indexes and results of pathological examination. Results （1） The carcinogenicity was 100% after 10 weeks. （2） The relatively suitable therapeutic dose of intravesical administration of 125^I-UdR was 37.5 MBq/kg in tumor-bearing rat blader. It was mainly detained in tumor-bearing rat bladder tumor and bladder wall around tumor after intravesical administration of 125^I -UdR,trace of it distributed in liver,spleen,kidney and lung. The changes of hemogram and biochemistry indexes were not observed,no significant pathological changes were found with normal organs after intravesical administration of 125^I-UdR in tumor-bearing rat bladder. Conclusion The results suggest that therapeutic application of 125^I-UdR （37.5 MBq/kg） by intravesical instillation in tumor-bearing rat bladder be safe and feasible.