Biodistribution of [125I]-labeled therapeutic proteins: Application in protein drug development beyond oncology*

The majority of biodistribution studies of therapeutic proteins published to date focus on tumor-targeting agents. In this report we present a number of case studies that demonstrate the utility of biodistribution studies during preclinical development of biotherapeutics for non oncology indications, as well as provide a practical perspective on the methodology applied to these studies. For the commonly used classes of biologics (such as human monoclonal antibodies), biodistribution profiles may be compared to those of other therapeutics of the same class and compounds with unexpected off-target mediated uptake may be identified. Temporal biodistribution profiles may be used to address kinetics and reversibility of target- and/or off-target-mediated accumulation. In cases when circulating biotherapeutic is rapidly eliminated from circulation due to the formation of anti-product antibodies, tissue data may provide useful insight on test article exposure at the site of therapeutic action (or at the site of toxicity). Comparison of temporal biodistribution profiles between the genetically engineered and wild-type mouse strains or between the disease models and healthy animals may provide useful insight on sites and kinetics of target-mediated elimination. Finally, biodistribution studies will be a useful tool to study in vivo disposition for a variety of existing and upcoming novel classes of protein compounds. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1028-1045, 2010