Synthesis and biodistribution of 99Tcm-Cetuximab antibody for lung tumor targeted molecular imaging

Abstract

Objective To prepare and evaluate 99Tcm radiolabeled Cetuximab (C225) for imaging of EGFR specific binding. Methods Cetuximab antibody was reduced by 2-iminothiophene (2-IT). The radiolabeling of IT-Cetuximab with 99Tcm (99Tcm-IT-Cetuximab) was analyzed by HPLC, and was tested for in vitro stability and molecular integrity. The human lung cancer line (A549)-bearing nude mouse model was prepared for biodistribution and tumor targeted study. Tumor uptake was also measured by in vivo γ imaging. Results The labeling efficiency was 93.15%. The radiochemical purity was 96.46% after purification. The in vitro stability was good in 5% HSA, in which the radiochemical purity maintained above 80% at 4 ℃ for 24 h. 99Tcm-IT-Cetuximab showed good specific binding to tumor with peak uptake of (3.417±0.769) %ID/g after 4 h. The T/NT ratio of blood increased to 1.454±0.174 at 24 h. γ imaging of A549-bearing nude mice xenografts also showed high T/NT ratio. Conclusions 99Tcm-IT-Cetuximab molecular probe could be prepared with high radiolabeling yield and radiochemical purity. It has excellent in vitro and in vivo stability, and shows specific uptake in A549 tumor. Key words: Lung neoplasms; Antibodies, monoclonal; Receptors, epidemal growth factor-urogastrone; Radionuclide imaging; Mice, nude