RADIOLABELED IODODEOXYURIDINE - SAFETY EVALUATION

Citation
Ka. Harrison et al., RADIOLABELED IODODEOXYURIDINE - SAFETY EVALUATION, The Journal of nuclear medicine, 37(4), 1996, pp. 13-16
Citations number
13
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging
ISSN journal
01615505
Volume
37
Issue
4
Year of publication
1996
Supplement
S
Pages
13 - 16
Database
ISI
SICI code
0161-5505(1996)37:4<13:RI-SE>2.0.ZU;2-Y
Abstract
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.