Journal article
Molecular imaging of death receptor 5 occupancy and saturation kinetics in vivo by humanized monoclonal antibody CS-1008
IJG Burvenich, FT Lee, GA Cartwright, GJ O'Keefe, D Makris, D Cao, S Gong, AC Chueh, JM Mariadason, MW Brechbiel, RA Beckman, K Fujiwara, R Von Roemeling, AM Scott
Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2013
Abstract
Purpose: CS-1008 (tigatuzumab; phase I/II), an antihuman death receptor 5 (DR5) agonist, induces apoptosis and has cytotoxic activity against human cancer cell lines. This study reports on the preclinical validation of 111In-labeled anti-DR5 humanized antibody CS-1008 as a diagnostic tool to study the DR5 occupancy in patients with cancer and establish dose ranges for receptor saturation kinetics in vivo. Experimental Design: CS-1008 was radiolabeled and characterized for DR5 binding and labeling efficiency on TRAIL-sensitive DR5-positive colorectal cancer cells (COLO 205 and WiDr). Pharmacokinetic and biodistribution studies were conducted in BALB/c nu/nu mice bearing COLO 205, WiDr, or DR5..
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Awarded by National Cancer Institute
Funding Acknowledgements
This work was financially supported by Daiichi Sankyo Co. Ltd. Operational Infrastructure Support Program funding was also provided by the Victorian Government. This research was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Centre for Cancer Research.