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

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.

• Authors: Liza Lindenberg, Anish Thomas, Stephen Adler, Esther Mena, Karen Kurdziel, Julia Maltzman, Bruce Wallin, Kimberly Hoffman, Ira Pastan, Chang Hum Paik, Peter Choyke, Raffit Hassan
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 6 Pg. 4496-504 (Feb 28 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25756664 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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