Oncotarget

Clinical Research Papers:

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

Catherina Willemien Menke-van der Houven, Elske C Gootjes, Marc C Huisman, Danielle J Vugts, Chantal Roth, Anne Marije Luik, Emma R Mulder, Robert C Schuit, Ronald Boellaard, Otto S Hoekstra, Guus AMS van Dongen and Henk MW Verheul _

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Oncotarget. 2015; 6:30384-30393. https://doi.org/10.18632/oncotarget.4672

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Abstract

Catharina Willemien Menke-van der Houven van Oordt1,*, Elske C. Gootjes1,*, Marc C. Huisman2, Danielle J. Vugts2, Chantal Roth1, Anne Marije Luik1, Emma R. Mulder2, Robert C. Schuit2, Ronald Boellaard2, Otto S. Hoekstra2, Guus AMS van Dongen2, Henk M.W. Verheul1

1Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

2Dept 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, 89zirconium, 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 89Zr-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 89Zr-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 89Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with 89Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without 89Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-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.


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