title: 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.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Liza
authors.initials: L
authors.lastname: Lindenberg
authors.affiliation: Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Anish
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Molecular Imaging Program, National Cancer Institute, SAIC-Frederick, Inc, NCI-Frederick, Frederick, MD, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Adler
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Mena
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Kurdziel
authors.affiliation: Morphotek, Exton, PA, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Maltzman
authors.affiliation: Morphotek, Exton, PA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Wallin
authors.affiliation: Morphotek, Exton, PA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Hoffman
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.affiliation: Radiology and Imaging Sciences, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Chang Hum
authors.initials: CH
authors.lastname: Paik
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.affiliation: Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Raffit
authors.initials: R
authors.lastname: Hassan
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging*; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; C526187:amatuximab; D000090204:Mesothelin