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.
Highlights
IntroductionMalignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura
Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura.It is a rare and aggressive malignancy, usually associated with continuous occupational exposure to asbestos, others etiological factors including iron, the simian virus 40 (SV40), and radiation [1,2,3,4]
Nimotuzumab (h-R3), an anti-epidermal growth factor receptor (EGFR) humanized antibody, has shown promising results in the treatment of head and neck, glioma, lung, pancreatic, and gastric cancers [24,25]. This agent has shown a good toxicity profile with a low incidence of adverse events [26,27,28]. These results suggest exploring the use of nimotuzumab in the treatment of MPM
Summary
Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, usually associated with continuous occupational exposure to asbestos, others etiological factors including iron, the simian virus 40 (SV40), and radiation [1,2,3,4]. Its main characteristic is an aggressive progression in almost all cases and a subsequent poor prognosis [1]. This tumor shows low chemo and radio-sensitivity [4]. A multimodal-approach based on surgical resection and a combination of chemotherapy and radiation has shown some benefits. The best response in patients has been found when combinations of chemotherapeutics are prescribed, mainly cisplatin and pemetrexed [5,6,7,8,9,10]
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