title: Local and systemic toxicity of h-R3, an anti-epidermal growth factor receptor monoclonal antibody, labeled with 188osmiun after the intracerebral administration in rats.
abstract: h-R3 is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb). This receptor is over-expressed in the majority of tumors of epithelial origin, including glioblastomas. 188Rhenium (188Re) constitutes an ideal radionuclide for imagining and radioimmunotherapy, and its toxicity is known, nevertheless, it is unknown if 188Os, as 188Re's daughter, has any local or systemic toxicity effect when it is administered intracerebrally for treating intracranial tumors. For this reason we decided to assess the toxicity of stable 188Os once the complete decay of 188Re has occurred, by administering intracerebrally to rats the h-R3 labeled with 188Os. Forty rats (20 each sex) were distributed randomly into four experimental groups (ten per group): control group received 5microL of glucoheptonate solution vehicle; two other groups were treated with unlabeled or labeled h-R3 with 188Os. The remaining group served as a non-treated control group. A single 5 microL dose (2.5 microL into each lateral ventricle) of neutral solution containing 50 microg of h-R3 labeled initially with 13.25 microCi of 188Re was stereotactically administered into lateral ventricles 8 days after the conjugation with the radionuclide was done. Each animal was observed daily for detection of toxicity signs. Body weights were recorded on days 0, 7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out at the end of the study. All animals gained weight by day 14. There were no changes in hematological and clinical chemistry, but minimal histopathological changes were observed at the application sites. This study shows that single doses of 188Os-h-R3 is tolerable and causes minimal local and no systemic toxicity effects in rats.
authors.affiliation: National Center for Breeding of Laboratory Animals, Havana, Cuba.
authors.forename: Barbara Gonzalez
authors.initials: BG
authors.lastname: Navarro
authors.forename: Angel Casacó
authors.initials: AC
authors.lastname: Parada
authors.forename: Pio
authors.initials: P
authors.lastname: Alvarez
authors.forename: Avelina
authors.initials: A
authors.lastname: Leon
authors.forename: Edilis
authors.initials: E
authors.lastname: Santana
authors.forename: Ana
authors.initials: A
authors.lastname: Bada
authors.forename: Rene
authors.initials: R
authors.lastname: Figueredo
authors.forename: Normando
authors.initials: N
authors.lastname: Iznaga-Escobar
authors.forename: Rolando
authors.initials: R
authors.lastname: Perez
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D066246:ErbB Receptors / Q000276:immunology; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D009992:Osmium / Q000008:administration & dosage / Q000633:toxicity*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D009992:Osmium; D066246:ErbB Receptors