89Zr-cetuximab PET imaging in patients with advanced colorectal cancer

// Catharina Willemien Menke-van der Houven van Oordt 1, * , Elske C. Gootjes 1, * , Marc C. Huisman 2 , Danielle J. Vugts 2 , Chantal Roth 1 , Anne Marije Luik 1 , Emma R. Mulder 2 , Robert C. Schuit 2 , Ronald Boellaard 2 , Otto S. Hoekstra 2 , Guus AMS van Dongen 2 , Henk M.W. Verheul 1 1 Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands 2 Dept of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands * These authors have contributed equally to this work Correspondence to: Henk M.W. Verheul, e-mail: h.verheul@vumc.nl Keywords: immunoPET, cetuximab, colorectal cancer, 89 zirconium, treatment selection Received: April 23, 2015      Accepted: July 10, 2015      Published: July 23, 2015 ABSTRACT Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of 89 Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq 89 Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients 89 Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with 89 Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without 89 Zr-cetuximab uptake. Taken together, tumor uptake of 89 Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC.