Safety and biodistribution of 111In-amatuximab in patients with mesothelin expressing cancers using single photon emission computed tomography-computed tomography (SPECT-CT) imaging

Oncotarget. 2015 Feb 28;6(6):4496-504. doi: 10.18632/oncotarget.2883.

Abstract

Amatuximab is a chimeric high-affinity monoclonal IgG1/k antibody targeting mesothelin that is being developed for treatment of mesothelin-expressing cancers. Considering the ongoing clinical development of amatuximab in these cancers, our objective was to characterize the biodistribution, and dosimetry of 111Indium (111In) radiolabelled amatuximab in mesothelin-expressing cancers. Between October 2011 and February 2013, six patients including four with malignant mesothelioma and two with pancreatic adenocarcinoma underwent Single Photon Emission Computed Tomography-Computed Tomography (SPECT/CT) imaging following administration of 111In amatuximab. SPECT/CT images were obtained at 2-4 hours, 24-48 hours and 96-168 hours after radiotracer injection. In all patients, tumor to background ratios (TBR) consistently met or exceeded an uptake of 1.2 (range 1.2-62.0) which is considered the minimum TBR that can be visualized. TBRs were higher in tumors of patients with mesothelioma than pancreatic adenocarcinoma. 111In-amatuximab uptake was noted in both primary tumors and metastatic sites. The radiotracer dose was generally well-tolerated and demonstrated physiologic uptake in the heart, liver, kidneys and spleen. This is the first study to show tumor localization of an anti-mesothelin antibody in humans. Our results show that 111In-amatuximab was well tolerated with a favorable dosimetry profile. It localizes to mesothelin expressing cancers with a higher uptake in mesothelioma than pancreatic cancer.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnostic imaging*
  • Aged
  • Antibodies, Monoclonal / pharmacokinetics*
  • Female
  • GPI-Linked Proteins / metabolism*
  • Humans
  • Indium Radioisotopes / pharmacokinetics
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / metabolism
  • Male
  • Mesothelioma / diagnostic imaging*
  • Mesothelioma / metabolism
  • Mesothelioma, Malignant
  • Middle Aged
  • Pancreatic Neoplasms / diagnostic imaging*
  • Radiopharmaceuticals / pharmacokinetics*
  • Tomography, Emission-Computed, Single-Photon / methods

Substances

  • Antibodies, Monoclonal
  • GPI-Linked Proteins
  • Indium Radioisotopes
  • Radiopharmaceuticals
  • amatuximab
  • mesothelin