Clinical Research Papers:
Safety and biodistribution of 111In-amatuximab in patients with mesothelin expressing cancers using single photon emission computed tomography-computed tomography (SPECT-CT) imaging
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Liza Lindenberg1,*, Anish Thomas2,*, Stephen Adler3, Esther Mena4, Karen Kurdziel1, Julia Maltzman5, Bruce Wallin5, Kimberly Hoffman5, Ira Pastan6, Chang Hum Paik7, Peter Choyke1, Raffit Hassan2
1Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
2Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
3Molecular Imaging Program, National Cancer Institute, SAIC-Frederick, Inc, NCI-Frederick, Frederick, MD, USA
4Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA
5Morphotek, Exton, PA, USA
6Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
7Radiology and Imaging Sciences, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA
*These authors have contributed equally to this work
Raffit Hassan, e-mail: [email protected]
Keywords: 111In-Amatuximab, radioimmunoconjugates, mesothelioma, pancreatic cancer, mesothelin
Received: December 04, 2014 Accepted: December 09, 2014 Published: February 04, 2015
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.
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