Experimental Study Of Bladder Cancer Internal Radiation By 5-[～(125)I]iodo-2'-deoxyuridine

Purpose: To study the pharmacokinetics and tissue distribution after intravesical instillation of 5-[¹²⁵I]iodo-2'-deoxyuridine (¹²⁵I-UdR) in normal rat bladder. To investigate the distribution and safety of ¹²⁵I-UdR in rat bearing bladder cancer. The properties and possibilities of application of intravesical instillation ¹²⁵I-UdR to rat bladder cancer were explored. Methods: (1) Two group of rats were given intravesical instillation and intravenous injection of ¹²⁵I-UdR separately. Serial blood samples were taken and measured by γscintillation counter. At different hour points after instillation, rats of the correspondent group were killed respectively, and radioactivity of various parts of organs was counted. (2) a double-weekly doses of 2mg N-methy1-N-nitrosourea (MNU) each time for 4 times intravesicular administration were given. (3) A relatively suitable therapeutic dose was obtained through analyzing levels of normal tissue injury by different dose of ¹²⁵I-UdR which was instilled intravesically in tumor-bearing rat bladder. The distribution of ¹²⁵I-UdR was estimated by SPECT scintigrams and analyzing the radioactivity of various organs determined by γscintillation counter after intravesical instillation of ¹²⁵I-UdR . The pharmic safety of tumor-bearing rat was evaluated by analyzing hemogram, biochemistry indexes and results of pathological examination. Results: (1) The results show that concentration-time curves after intravesical instillation are fitted to a 2-compartment model. After intravesical instillation of 100μg/kg 125I-UdR expressed as chemical dose , The average of T1/2βis 36.78h, Cmax is 0.54μg/L, Tmax is 1.72h. After intravenous injection of 100μg/kg 125I-UdR expressed as chemical dose , The average of T1/2 is 0.09h , Cmax is 14.55μg/L, Tmax is 0.00h , the absolute bioavailability F is 38.46% by intravesial administration of 125I-UdR in normal rat bladder. After intravesical instillation of 125I-UdR in normal rats bladder, it was more absorbed in bladder than in other organs. (2) The rat of carcinogenicity was 100% after 10 weeks. (3)The relatively suitable therapeutic dose of intravesical administration of 125I-UdR was 37.5MBq/kg in tumor-bearing rat bladder. It was mainly detained in tumor-bearing rat bladder tumor and bladder wall around tumor after intravesical administration of 125I-UdR , trace of it diatributed in liver, spleen, kidney, lung. The changes of hemogram and biochemistry indexes were not observed, no significant pathological changes were found with normal organs after intravesical administration of 125I-UdR in tumor-bearing rat bladder. Conclusions: (1) 125I-UdR used for the intravesical instillation could improve the drug concentration of 125I-UdR in local tissues, prolong the acting time in target organ (bladder) and reduce the side-effect to surrounding tissues. 125I-UdR is a promising agent in treating of bladder cancer. (2) The results suggest the safety and feasibility of therapeuticapplication of 125I-UdR(37.5MBq/kg) by intravesical instillation in tumor-bearing rat bladder. (3) The method to induce bladder tumor by intravesicular administration of MNU is convenient and reliable.