RESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacocinética , Radioisótopos de Galio/farmacocinética , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Neoplasias Pleurales/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Línea Celular Tumoral , Fluorodesoxiglucosa F18/química , Humanos , Imagenología Tridimensional , Hígado/metabolismo , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Mesotelioma/diagnóstico por imagen , Mesotelioma Maligno , Ratones Desnudos , Neoplasias Pleurales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
In this paper, we report the conjugation of the humanized monoclonal antibody nimotuzumab with cisplatin-loaded liposomes and the in vitro evaluation of its affinity for tumor cells. The conjugation procedure was performed through derivatization of nimotuzumab with N-succinimidyl S-acetylthioacetate (SATA) followed by a covalent attachment with maleimide groups at the end of PEG-DSPE chains located at the membrane of pre-formed liposomes. Confocal microscopy was performed to evaluate the immunoliposome affinity for EGFR antigens from human epidermoid carcinoma (A-431) and normal lung (MRC-5) cell lines. Results showed that the procedures implemented in this work do not affect the capability of the nimotuzumab-immunoliposomes to recognize the tumor cells, which overexpress the EGFR antigens.