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 123I or 125I (*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).


CONCLUSIONS
Since this carrier of Auger electron emitters has antineoplastic effects ([123I]IUdR and [125I]IUdR) in addition to its scintigraphic potential ([123I]IUdR and [131I]IUdR), it holds promise for therapy and early diagnosis of bladder cancer.
Van den Abbeele
A D
AD
Department of Radiology (Nuclear Medicine), Harvard Medical School, Boston, Massachusetts, USA.
Tutrone
R F
RF
Berman
R M
RM
Baranowska-Kortylewicz
J
J
Barclay
P D
PD
Richie
J P
JP
Adelstein
S J
SJ
Kassis
A I
AI
D000818:Animals; D001345:Autoradiography; D002273:Carcinogens; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D005260:Female; D007065:Idoxuridine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008770:Methylnitrosourea; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014018:Tissue Distribution; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000532:radiotherapy*
D002273:Carcinogens; D007457:Iodine Radioisotopes; D008770:Methylnitrosourea; D007065:Idoxuridine