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Malignant mesothelioma (MM), a rare form of cancer is often associated with previous exposure to fibrous minerals, such as asbestos. Asbestos exposure increases HER1-activity and expression in pre-clinical models. Additionally, HER1 over-expression is observed in the majority of MM cases. In this study, the utility of HER1-targeted chimeric IgG 1 , cetuximab, and a human IgG 2 , panitumumab, radiolabeled with  86 Y, were evaluated for PET imaging to detect MM non-invasively  in vivo , and to select an antibody candidate for radioimmunotherapy (RIT).    Methods  Radioimmunoconjugates (RICs) of cetuximab and panitumumab were prepared by conjugation with CHX-A’’-DTPA followed by radiolabeling with  86 Y. The HER1 expression of NCI-H226, NCI-H2052, NCI-H2452 and MSTO-211H human mesothelioma cells was characterized by flow cytometry.  In vivo  biodistribution, pharmacokinetic analysis, and PET imaging were performed in tumor bearing athymic mice.    Results    In vivo  studies demonstrated high HER1 tumor uptake of both RICs. Significant reduction in tumor uptake was observed in mice co-injected with excess mAb (0.1 mg), demonstrating that uptake in the tumor was receptor specific. Significant differences were observed in the  in vivo  characteristics of the RICs. The blood clearance T ½ α of  86 Y-cetuximab (0.9–1.1 h) was faster than  86 Y-panitumumab (2.6–3.1 h). Also, the tumor area under the curve (AUC) to liver AUC ratios of  86 Y-panitumumab were 1.5 to 2.5 times greater than  86 Y-cetuximab as observed by the differences in PET tumor to background ratios, which could be critical when imaging orthotopic tumors and concerns regarding radiation doses to normal organs such as the liver.    Conclusion  This study demonstrates the more favorable HER1-targeting characteristics of  86 Y-panitumumab than  86 Y-cetuximab for non-invasive assessment of the HER1 status of MM by PET imaging. Due to lower liver uptake, panitumumab based immunoconjugates may fare better in therapy than corresponding cetuximab based immunoconjugates.

plos one

HER1-Targeted 86Y-Panitumumab Possesses Superior Targeting Characteristics than 86Y-Cetuximab for PET Imaging of Human Malignant Mesothelioma Tumors Xenografts