Harrison K A, Dalrymple G V, Baranowska-Kortylewicz J, Holdeman K P, Schneiderman M H, Lieberman R P, Sharp J G, Cohen S M, Leichner P K, Augustine S C, Tempero M A, Taylor R J, Chiou R K
Department of Radiology, University of Nebraska Medical Center, Omaha 68198-1045, USA.
J Nucl Med. 1996 Apr;37(4 Suppl):13S-16S.
The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration.
Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained.
To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation.
When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.
