Cumulated Activity Comparison of 64Cu-/177Lu-Labeled Anti-Epidermal Growth Factor Receptor Antibody in Esophageal Squamous Cell Carcinoma Model

J Nucl Med. 2017 Jun;58(6):888-890. doi: 10.2967/jnumed.116.180521. Epub 2017 Jan 12.

Abstract

This work aimed at estimating the kinetic parameters, and hence cumulated activity (AC), of a diagnostic/therapeutic convergence radiopharmaceutical, namely 64Cu-/177Lu-labeled antibody (64Cu-/177Lu-cetuximab), that acts as anti-epidermal growth factor receptor. Methods: In mice bearing esophageal squamous cell carcinoma tumors, to estimate uptake (K), release rate constant (kR), and hence AC, a kinetic model analysis was applied to recently published biodistribution data of immuno-PET imaging with 64Cu-cetuximab and of small-animal SPECT/CT imaging with 177Lu-cetuximab, including blood and TE-8 tumor. Results: K, kR, and AC were estimated to be 0.0566/0.0593 g⋅h-1⋅g-1, 0.0150/0.0030 h-1, and 2.3 × 1010/4.1 × 1012 disintegrations (per gram of TE-8 tumor), with an injected activity of 3.70/12.95 MBq, for 64Cu-/177Lu-cetuximab, respectively. Conclusion: A model is available for comparing kinetic parameters and AC of the companion diagnostic/therapeutic 64Cu-/177Lu-cetuximab that may be considered as a step for determining whether one can really use the former to predict dosimetry of the latter.

Keywords: 177Lu-labeled SPECT tracer; 64Cu-labeled PET tracer; EGFR; cumulated activity; kinetic model analysis.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics*
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Computer Simulation
  • Copper Radioisotopes / pharmacokinetics*
  • ErbB Receptors / metabolism*
  • Esophageal Neoplasms / diagnostic imaging
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Lutetium / pharmacokinetics*
  • Metabolic Clearance Rate
  • Mice
  • Models, Biological
  • Positron-Emission Tomography / methods
  • Radiation Dosage
  • Radioisotopes / pharmacokinetics
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Copper Radioisotopes
  • Radioisotopes
  • Radiopharmaceuticals
  • Lutetium
  • ErbB Receptors