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Molecules ; 23(12)2018 Nov 29.
Article in English | MEDLINE | ID: mdl-30501113

ABSTRACT

Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacokinetics , Gallium Radioisotopes/pharmacokinetics , Lung Neoplasms/metabolism , Mesothelioma/metabolism , Pleural Neoplasms/metabolism , Xenograft Model Antitumor Assays , Animals , Cell Line, Tumor , Fluorodeoxyglucose F18/chemistry , Humans , Imaging, Three-Dimensional , Liver/metabolism , Lung Neoplasms/diagnostic imaging , Male , Mesothelioma/diagnostic imaging , Mesothelioma, Malignant , Mice, Nude , Pleural Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography , Tissue Distribution , Tomography, Emission-Computed, Single-Photon
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