No abstract

Radiolabeled antiangiogenic monoclonal antibodies are potential agents for targeted therapy in specific types of malignancies. In this study, (166)Ho-DOTA-Bevacizumab was used in biodistribution studies using single-photon emission computed tomography (SPECT) to acquire dosimetric aspects of the radiolabeled antibody in mice. The liver toxicity of the radiolabeled antibody was also determined using serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase and alkaline phosphatase assay 2-7 days post-injection. The SPECT biodistribution demonstrated a similar pattern as the other radiolabeled anti-vascular endothelial growth factor A (VEGF-A) immunoconjugates. (166)Ho-DOTA-Bevacizumab was revealed as a potential compound for therapy/imaging of VEGF-A expression in oncology.

Summary In this study, bevacizumab was successively labeled with 111In-InCl3 after conjugation with DOTA-NHS-ester followed by molecular filtration and determination of the average number ofDOTAconjugated per mAb (6 : 1) by spectrophotometric method. Radiochemical purity (> 97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of 111In-DOTA-Bevacizumab (in final formulation, human serum, liver/kidney homogenates) were determined in 24-72 h as well as biodistribution studies in wild-type rats and human colon cancer (SW-480) bearing mice. The accumulation of the radiolabeled antibody was consistent with the former reported Bevacizumab conjugates. Significant tumor uptake (8%) was observed at 72 h p.i. Tumor/muscle uptake ratios were 2.6 (24 h), 9.74 (48 h) and 25 (72 h). 111In- DOTA-Bevacizumab was prepared as a SPECT molecular imaging agent for diagnosis and follow-up of vascular endothelial growth factor A (VEGF-A) expression in oncology.