Abstract 2446: Biodistribution of antibody drug conjugates by LC-MS

Abstract

Abstract Introduction: A method to study biodistribution of adduct forming antibody drug conjugates (ADCs) by LC-MS Description: ADCs are increasingly used to deliver cytotoxic payloads to tumor cells. While the targeted approach has vastly improved the toxicity profiles of these drugs, it is still important to understand the bio-distribution and the enhanced tumor localization this approach offers. Radio-labeled methods are still the most reliable approach to study the bio-distribution, but may not be able to differentiate between the drug that is present in the tissue from those that have formed covalent adducts upon non-specific internalization. Here, we describe a mass-spectrometric methods to identify these covalent adducts these cytotoxic agents form and how such methods could be utilized to map the bio-distribution in xenograft models. Data: The antibody drug conjugate is highly localized in the tumor with a %ID/gm value of almost 40 within 24 hours of dosing and no non-specific accumulation in other organs observed. Conclusions: A simple and robust LC-MS based method has been developed to understand the bio-distribution of antibody-drug conjugates by detecting and quantifying the actual and final chemical state of the toxin in the targeted cell. This method could be used to evaluate the (1) PK of antibody-drug conjugates (2) make lead selections at advanced preclinical stages of antibody-drug development (3) understand the ADME properties of the chosen antibody-drug conjugate Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2446.