TUMOR UPTAKE AND MITOTIC-ACTIVITY PATTERN OF 5-[I-125]IODO-2'-DEOXYURIDINE AFTER INTRAVESICAL INFUSION IN PATIENTS WITH BLADDER-CANCER

In patients with bladder cancer, little is known about diffusion in th e tumor mass of 5-iodo-2'-deoxyuridine (IUdR) administered intralumina lly, although previous studies based on external scanning have shown p romising tumor-targeting properties of IUdR instilled intravesically, This study compared the pattern of IUdR uptake by bladder cancer cells with the actual distribution of mitotic activity, as evaluated by inc ubation of ex vivo tumor specimens with tritiated thymidine, Methods: The [I-125]IUdR (2-13 MBq) was instilled over 1-3 hr in the bladder of four patients with bladder cancer scheduled for ablative surgery. Twe nty-four hours later, surgical samples were assayed for radioactivity and processed for microautoradiography, while fresh tumor specimens we re fragmented, incubated with [H-3]thymidine and further processed for microautoradiography. The diffusion of labeled IUdR across the bladde r wall was evaluated by blood sampling, Results: Tumor incorporation o f [(125)]]IUdR 24 hr after intravesical instillation was 0.002%-0.05% ID/g, while the average tumor-to-normal bladder ratio was about 20, Mi croautoradiography showed that [I-125]IUdR incorporation was confined to tumor cells in the most superficial layers of the bladder, while in cubation of the tumor fragments with [H-3]thymidine demonstrated the p resence of diffuse mitotic activity also in the deeper tumor mass. Dif fusion of labeled IUdR in the general circulation was minimal. Conclus ion: Poor diffusion in the tumor mass makes IUdR unsuitable for intra cavitary therapy of bladder cancer, but the role of such an approach i n the postsurgical ''sterilization'' of cancer remnants floating in th e bladder lumen after partial cystectomy should be explored.