Synthesis, radiolabeling and quality control of ¹¹¹In-DOTA-bevacizumab for radioimmunoscintigraphy of VEGF receptors

Abstract

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.