Abstract
Tumor resistance to treatment paved the way toward the development of single agent drugs that target multiple molecular signatures amplified within the malignancy. The discovered crosstalk between EGFR and HER3 as well as the role of HER3 in mediating EGFR resistance made these two receptor tyrosine kinases attractive targets. MEHD7945A or duligotuzumab is a single immunotherapy agent that dually targets both molecular signatures. In this study, a positron emission tomography (PET) companion diagnostic to MEHD7945A is reported and evaluated in pancreatic cancer. Tumor accretion and whole body pharmacokinetics of 89Zr-MEHD7945A were established. Specificity of the probe for EGFR and/or HER3 was further examined.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Monoclonal / chemistry
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Antibodies, Monoclonal / pharmacokinetics
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Antibodies, Monoclonal / pharmacology
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / metabolism
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Female
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Humans
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Immunoglobulin G / chemistry
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Immunoglobulin G / pharmacology*
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Mice, SCID
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Pancreatic Neoplasms / diagnostic imaging
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / therapy*
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Positron-Emission Tomography / methods*
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Radioisotopes / chemistry
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Receptor, ErbB-3 / antagonists & inhibitors*
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Receptor, ErbB-3 / metabolism
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Xenograft Model Antitumor Assays
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Zirconium / chemistry
Substances
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Antibodies, Monoclonal
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Antineoplastic Agents
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Immunoglobulin G
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MEHD7945A
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Radioisotopes
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Zirconium
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EGFR protein, human
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ErbB Receptors
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Receptor, ErbB-3
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Zirconium-89