Safety and biodistribution of 111In-amatuximab in patients with mesothelin expressing cancers using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging
| Autor: | Julia D. Maltzman, Stephen Adler, Ira Pastan, Bruce A. Wallin, Raffit Hassan, Chang Hum Paik, Peter L. Choyke, Kimberly Hoffman, Anish Thomas, Esther Mena, Karen A. Kurdziel, Liza Lindenberg |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Mesothelioma medicine.medical_specialty Lung Neoplasms pancreatic cancer Amatuximab Adenocarcinoma Single-photon emission computed tomography GPI-Linked Proteins Pancreatic cancer Humans Medicine Mesothelin Aged Tomography Emission-Computed Single-Photon radioimmunoconjugates biology medicine.diagnostic_test business.industry Indium Radioisotopes Mesothelioma Malignant Antibodies Monoclonal Cancer mesothelin Middle Aged medicine.disease Pancreatic Neoplasms Oncology Monoclonal biology.protein Female Radiology Clinical Research Paper Radiopharmaceuticals 111In-Amatuximab business Nuclear medicine |
| Zdroj: | Oncotarget Scopus-Elsevier |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.2883 |
| Popis: | // Liza Lindenberg 1, * , Anish Thomas 2, * , Stephen Adler 3 , Esther Mena 4 , Karen Kurdziel 1 , Julia Maltzman 5 , Bruce Wallin 5 , Kimberly Hoffman 5 , Ira Pastan 6 , Chang Hum Paik 7 , Peter Choyke 1 , Raffit Hassan 2 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 2 Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 3 Molecular Imaging Program, National Cancer Institute, SAIC-Frederick, Inc, NCI-Frederick, Frederick, MD, USA 4 Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA 5 Morphotek, Exton, PA, USA 6 Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 7 Radiology and Imaging Sciences, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA * These authors have contributed equally to this work Correspondence to: Raffit Hassan, e-mail: hassanr@mail.nih.gov Keywords: 111 In-Amatuximab, radioimmunoconjugates, mesothelioma, pancreatic cancer, mesothelin Received: December 04, 2014 Accepted: December 09, 2014 Published: February 04, 2015 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 111 Indium ( 111 In) 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 111 In 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. 111 In-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 111 In-amatuximab was well tolerated with a favorable dosimetry profile. It localizes to mesothelin expressing cancers with a higher uptake in mesothelioma than pancreatic cancer. |
| Databáze: | OpenAIRE |
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