Tumor-targeting potential of radioiodinated iododeoxyuridine in bladder cancer

J Nucl Med. 1996 Feb;37(2):315-20.

Abstract

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).

Conclusion: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoradiography
  • Carcinogens
  • Carcinoma, Transitional Cell / chemically induced
  • Carcinoma, Transitional Cell / diagnostic imaging
  • Carcinoma, Transitional Cell / radiotherapy*
  • Female
  • Idoxuridine / pharmacokinetics
  • Idoxuridine / therapeutic use*
  • Iodine Radioisotopes / pharmacokinetics
  • Iodine Radioisotopes / therapeutic use*
  • Methylnitrosourea
  • Radionuclide Imaging
  • Rats
  • Rats, Inbred F344
  • Time Factors
  • Tissue Distribution
  • Urinary Bladder Neoplasms / chemically induced
  • Urinary Bladder Neoplasms / diagnostic imaging
  • Urinary Bladder Neoplasms / radiotherapy*

Substances

  • Carcinogens
  • Iodine Radioisotopes
  • Methylnitrosourea
  • Idoxuridine