title: 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer.
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 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.
authors: Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Catharina Willemien
authors: CW
authors: Menke-van der Houven van Oordt
authors: Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Elske C
authors: EC
authors: Gootjes
authors: Dept of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Marc C
authors: MC
authors: Huisman
authors: Dept of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Danielle J
authors: DJ
authors: Vugts
authors: Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Chantal
authors: C
authors: Roth
authors: Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Anne Marije
authors: AM
authors: Luik
authors: Dept of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Emma R
authors: ER
authors: Mulder
authors: Dept of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Robert C
authors: RC
authors: Schuit
authors: Dept of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Ronald
authors: R
authors: Boellaard
authors: Dept of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Otto S
authors: OS
authors: Hoekstra
authors: Dept of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Guus Ams
authors: GA
authors: van Dongen
authors: Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Henk M W
authors: HM
authors: Verheul
mesh_terms: D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000068818:Cetuximab / Q000008:administration & dosage* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D049268:Positron-Emission Tomography / Q000379:methods*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011868:Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D016896:Treatment Outcome; D015040:Zirconium / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015040:Zirconium; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: 89zirconium; cetuximab; colorectal cancer; immunoPET; treatment selection