Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft

Molecules. 2018 Nov 29;23(12):3138. doi: 10.3390/molecules23123138.

Abstract

Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.

Keywords: biomarkers; malignant pleural mesothelioma; molecular imaging; nimotuzumab; radioimmunoconjugates.

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Cell Line, Tumor
  • Fluorodeoxyglucose F18 / chemistry
  • Gallium Radioisotopes / pharmacokinetics*
  • Humans
  • Imaging, Three-Dimensional
  • Liver / metabolism
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / metabolism*
  • Male
  • Mesothelioma / diagnostic imaging
  • Mesothelioma / metabolism*
  • Mesothelioma, Malignant
  • Mice, Nude
  • Pleural Neoplasms / diagnostic imaging
  • Pleural Neoplasms / metabolism*
  • Positron Emission Tomography Computed Tomography
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Xenograft Model Antitumor Assays*

Substances

  • Antibodies, Monoclonal, Humanized
  • Gallium Radioisotopes
  • Fluorodeoxyglucose F18
  • Gallium-67
  • nimotuzumab