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

Oncotarget. 2015 Oct 6;6(30):30384-93. doi: 10.18632/oncotarget.4672.

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.

Keywords: 89zirconium; cetuximab; colorectal cancer; immunoPET; treatment selection.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Cetuximab / administration & dosage*
  • Cetuximab / metabolism
  • Colorectal Neoplasms / diagnostic imaging*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Disease Progression
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Mutation
  • Positron-Emission Tomography / methods*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Radioisotopes / administration & dosage*
  • Radioisotopes / pharmacokinetics
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution
  • Treatment Outcome
  • Zirconium / administration & dosage*
  • Zirconium / pharmacokinetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Radioisotopes
  • Radiopharmaceuticals
  • Zirconium
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • Cetuximab