title: Toxicity and biodistribution of an iodine-131-radiolabelled tumour necrosis-targeting antibody in non-tumour-bearing domestic felines.
abstract: The potential of human immunotherapeutics now revolutionizing modern cancer therapy has yet to make an impact in veterinary medicine, mainly due to the evolutionary differences between human and non-human cell surface antigens which bar the efficacy for many antibodies targeting human antigens. Here, we explore the possible use of an iodine-131 (I-131)-radiolabelled chimericTNT-1/B antibody, Cotara, being tested in humans, which targets a highly conserved structure present in all solid tumours. The goal was to document the possible toxic side-effects, retention, excretion and biodistribution of Cotara in non-tumour-bearing felines. The study was conducted with six lab animal domestic shorthaired felines. Two felines were randomly placed into three dose groups: 1.5, 2.0, and 3.0 mCi kg(-1) (0.68, 0.9 and 1.36 mCi lb(-1)); these doses were administered by a single IV injection. Thyroid blockade with potassium iodide (KI) was administered orally once daily. Over the 90-day study, haematologic test results, serum chemistry, thyroid function, food intake and morbidity were recorded. Drug distribution was ascertained through nuclear scintigraphy. Four of the six subjects had decreased appetite (Grade 1) that started on day 4 and then resolved by day 10. Two subjects exhibited intermittent days of anorexia (Grade 2) from day 5 to day 13. Both subjects with Grade 2 anorexia were sacrificed and necropsied once each exhibited two consecutive days of signs. Vomiting (Grade 2) occurred in 3 subjects from day 4 to day 13. Three subjects had moderate regenerative anaemia (Grade 2), whereas two developed leucocytosis. Overall, a single intravenous dose of Cotara resulted in moderate toxicity, with subjects exhibiting transitory signs of anorexia and vomiting without laboratory evidence of organ pathology. Each subject received a once daily oral dose of KI (33 mg) that was found to be safe and effective in the prevention of radiation damage to the thyroid gland over the study period. With a moderate toxicity profile, Cotara may hold unique promise by delivering I-131 directly into solid tumours of various types in felines.
authors.affiliation: Jersey-Calhoun Veterinary Hospital, Jerseyville, IL 62052, USA. donvw@hyprcat.com
authors.forename: D M
authors.initials: DM
authors.lastname: Van Walleghen
authors.forename: M H
authors.initials: MH
authors.lastname: Parseghian