her1-targeted 86y-panitumumab possesses superior targeting characteristics than 86y-cetuximab for pet imaging of human malignant mesothelioma tumors xenograftsher1-targeted 86 y-panitumumab拥有优越的目标特征比86 y-cetuximab人类恶性间皮瘤的pet成像肿瘤异种移植.pdfVIP

HER1-Targeted 86Y-Panitumumab Possesses Superior Targeting Characteristics than 86Y-Cetuximab for PET Imaging of Human Malignant Mesothelioma Tumors Xenografts Tapan K. Nayak*, Kayhan Garmestani, Diane E. Milenic, Kwamena E. Baidoo, Martin W. Brechbiel* Radioimmune Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America Abstract 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 IgG1, cetuximab, and a human IgG2, panitumumab, radiolabeled with 86Y, 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 86Y. 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 a of 86Y-cetuximab