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Imaging EGFR and HER3 through 89 Zr-labeled MEHD7945A (Duligotuzumab).
- Source :
-
Scientific reports [Sci Rep] 2018 Jun 13; Vol. 8 (1), pp. 9043. Date of Electronic Publication: 2018 Jun 13. - Publication Year :
- 2018
-
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 <superscript>89</superscript> Zr-MEHD7945A were established. Specificity of the probe for EGFR and/or HER3 was further examined.
- Subjects :
- Animals
Antibodies, Monoclonal chemistry
Antibodies, Monoclonal pharmacokinetics
Antibodies, Monoclonal pharmacology
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacokinetics
Antineoplastic Agents pharmacology
Cell Line, Tumor
ErbB Receptors antagonists & inhibitors
ErbB Receptors metabolism
Female
Humans
Immunoglobulin G chemistry
Mice, SCID
Pancreatic Neoplasms diagnostic imaging
Pancreatic Neoplasms metabolism
Radioisotopes chemistry
Receptor, ErbB-3 metabolism
Xenograft Model Antitumor Assays
Zirconium chemistry
Immunoglobulin G pharmacology
Pancreatic Neoplasms therapy
Positron-Emission Tomography methods
Receptor, ErbB-3 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29899472
- Full Text :
- https://doi.org/10.1038/s41598-018-27454-6