Tumor-targeting potential of radioiodinated iododeoxyuridine in bladder cancer

Since bladder cancer arises in the superficial lining of the urothelium, it is a likely candidate for site-directed administration of 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter I-123 or I-125 (*IUdR). Methods: We instilled *IUdR for 2 hr directly within the bladder lumen of rats bearing N-methyl-N-nitrosourea (NMU)-induced bladder cancer and conducted scintigraphic, biodistribution and autoradiography (ARG) studies 48 hr and 1 wk later. Control animals were not subjected to the carcinogen but were instilled with *IUdR. Results: Two groups of animals were identified after instillation of MNU: Group A consisted of rats with hyperplasia and Group B of rats with papillary carcinoma (stages Ta and T1). Scintigraphic detection of carcinomas was achieved with high sensitivity and specificity, and increased tumor-to-normal tissue ratios were obtained in both groups. Moreover, ARG demonstrated that (1) the uptake of *IUdR was observed in the hyperplastic and carcinomatous urothelium but not in the normal urothelium; (2) uptake was detected at a very early stage of tumor development (hyperplasia stage); (3) *IUdR was able to penetrate deep within the bladder wall; and (4) other normal dividing tissues, such as the bone marrow, the small intestine and the large intestine, were free of silver grains (i.e., no DNA-incorporated *IUdR). Conclusion: Since this carrier of Auger electron emitters has antineoplastic effects ([I-123]IUdR and [I-125]IUdR) in addition to its scintigraphic potential ([I-123]IUdR and [I-131]IUdR), it holds promise for therapy and early diagnosis of bladder cancer.