title: Biodistribution Analyses of a Near-Infrared, Fluorescently Labeled, Bispecific Monoclonal Antibody Using Optical Imaging.
abstract: In recent years, biodistribution analyses of pharmaceutical compounds in preclinical animal models have become an integral part of drug development. Here we report on the use of optical imaging biodistribution analyses in a mouse xenograft model to identify tissues that nonspecifically retained a bispecific antibody under development. Although our bispecific antibody bound both the epidermal growth factor receptor and insulin growth factor 1 receptor are expressed on H358, nonsmall-cell lung carcinoma cells, the fluorescence from labeled bispecific antibody was less intense than expected in xenografted tumors. Imaging analyses of live mice and major organs revealed that the majority of the Alexa Fluor 750 labeled bispecific antibody was sequestered in the liver within 2 h of injection. However, results varied depending on which near-infrared fluorophore was used, and fluorescence from the livers of mice injected with bispecific antibody labeled with Alexa Fluor 680 was less pronounced than those labeled with Alexa Fluor 750. The tissue distribution of control antibodies remained unaffected by label and suggests that the retention of fluorophores in the liver may differ. Given these precautions, these results support the incorporation of optical imaging biodistribution analyses in biotherapeutic development strategies.
authors.affiliation: Department of Translational Sciences, MedImmune, Gaithersburg, Maryland, USA. petersonn@medimmune.com.
authors.forename: Norman C
authors.initials: NC
authors.lastname: Peterson
authors.affiliation: Department of Translational Sciences, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: George G
authors.initials: GG
authors.lastname: Wilson
authors.affiliation: Department of Cancer Biology, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Dimasi
authors.affiliation: Departments of Cancer Biology, MedImmune, Gaithersburg, Maryland.
authors.forename: Kris F
authors.initials: KF
authors.lastname: Sachsenmeier
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D015195:Drug Design; D055808:Drug Discovery; D066246:ErbB Receptors; D005260:Female; D005456:Fluorescent Dyes; D008099:Liver / Q000473:pathology; D051379:Mice; D023421:Models, Animal; D061848:Optical Imaging; D019265:Spectroscopy, Near-Infrared; D013388:Succinimides; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: C502599:Alexa Fluor 750; D018033:Antibodies, Bispecific; D005456:Fluorescent Dyes; D013388:Succinimides; C512478:EGFR protein, human; D066246:ErbB Receptors