The emphasis of radiolabeled iododeoxyuridine (IUdR) research at our
institution to date has been to assess its safety as a potential thera
peutic agent. Toward this goal, we have performed preclinical and clin
ical studies, using various routes of administration, to detect advers
e changes in normal tissues in both humans and animals. As IUdR is rap
idly dehalogenated by the liver, the intravenous route is unlikely to
be successful in therapeutic efforts. We have therefore focused our at
tention on more ''protected'' routes: intra-arterial and intravesicula
r administration. Methods: Studies were performed in farm pigs after m
ultiple administrations of [(125)]IUdR into the aorta, carotid artery
and bladder. IUdR and metabolites were measured in venous blood sample
s at appropriate time intervals after administration, after which hist
ologic examination of tissues was performed. Studies in human have bee
n performed after intra-arterial administration of [I-123]IUdR in pati
ents with liver metastases and intravesicular administration in patien
ts with bladder carcinoma, initially using [I-123]IUdR and currently u
sing both [I-123]IUdR and [I-125]IUdR. Blood samples for pharmacokinet
ics and metabolite analysis and tissue for autoradiography (when feasi
ble) have been obtained, Results: To date, no evidence of adverse effe
cts on normal tissue or alteration of hematologic or metabolic indices
have been seen in pigs or humans. When instilled in the bladder, ther
e is little leakage of IUdR in the circulation. Conclusion: When [I-12
5]IUdR is used as a therapeutic agent, we anticipate little or no effe
ct on normal tissues.