Imaging the distribution of an antibody-drug conjugate constituent targeting mesothelin with ⁸⁹Zr and IRDye 800CW in mice bearing human pancreatic tumor xenografts

التفاصيل البيبلوغرافية
العنوان: Imaging the distribution of an antibody-drug conjugate constituent targeting mesothelin with ⁸⁹Zr and IRDye 800CW in mice bearing human pancreatic tumor xenografts
المؤلفون: Eva J, ter Weele, Anton G T, Terwisscha van Scheltinga, Jos G W, Kosterink, Linda, Pot, Silke R, Vedelaar, Laetitia E, Lamberts, Simon P, Williams, Marjolijn N, Lub-de Hooge, Elisabeth G E, de Vries
المصدر: Oncotarget
سنة النشر: 2015
مصطلحات موضوعية: Male, Cytoplasm, IRDye 800CW, Immunoconjugates, Indoles, Time Factors, endocrine system diseases, Transplantation, Heterologous, pancreatic cancer, zirconium-89, PET imaging, Mice, Nude, GPI-Linked Proteins, Cell Line, Tumor, parasitic diseases, Animals, Humans, Tissue Distribution, Radioisotopes, Mice, Inbred BALB C, Benzenesulfonates, Antibodies, Monoclonal, mesothelin, Immunohistochemistry, Pancreatic Neoplasms, Microscopy, Fluorescence, Positron-Emission Tomography, Zirconium, Research Paper
الوصف: Mesothelin is a tumor differentiation antigen expressed by epithelial tumors, including pancreatic cancer. Currently, mesothelin is being targeted with an antibody-drug conjugate (ADC) consisting of a mesothelin-specific antibody coupled to a highly potent chemotherapeutic drug. Considering the toxicity of the ADC and reduced accessibility of pancreatic tumors, non-invasive imaging could provide necessary information. We therefore developed a zirconium-89 (89Zr) labeled anti-mesothelin antibody (89Zr-AMA) to study its biodistribution in human pancreatic tumor bearing mice. Biodistribution and dose-finding of 89Zr-AMA were studied 144 h after tracer injection in mice with subcutaneously xenografted HPAC. MicroPET imaging was performed 24, 72 and 144 h after tracer injection in mice bearing HPAC or Capan-2. Tumor uptake and organ distribution of 89Zr-AMA were compared with nonspecific 111In-IgG. Biodistribution analyses revealed a dose-dependent 89Zr-AMA tumor uptake. Tumor uptake of 89Zr-AMA was higher than 111In-IgG using the lowest tracer dose. MicroPET showed increased tumor uptake over 6 days, whereas activity in blood pool and other tissues decreased. Immunohistochemistry showed that mesothelin was expressed by the HPAC and CAPAN-2 tumors and fluorescence microscopy revealed that AMA-800CW was present in tumor cell cytoplasm. 89Zr-AMA tumor uptake is antigen-specific in mesothelin-expressing tumors. 89Zr-AMA PET provides non-invasive, real-time information about AMA distribution and tumor targeting.
تدمد: 1949-2553
URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid________::1a411c31cff09eb37f9a552fdc2cccdd
https://pubmed.ncbi.nlm.nih.gov/26536664
حقوق: OPEN
رقم الأكسشن: edsair.pmid..........1a411c31cff09eb37f9a552fdc2cccdd
قاعدة البيانات: OpenAIRE