Synthesis and single photon emission computed tomography imaging evaluation with 99mTc-labeled bevacizumab in colorectal cancer xenografts

Objectives The aim of this study was to synthesize and non-invasively image in colorectal cancer xenografts with 99mTc-labeled anti-vascular endothelial growth factor A antibody (anti-VEGFA, 99mTc-MAG3-bevacizumab).

Methods Bevacizumab was labeled with [99mTc]TcO4- after conjugation with MAG3-NHS-ester and the radiolabeling conditions were optimized. The products were purified by molecular filtration (PD MidiTrap G-10 column). Biodistribution studies and single photon emission computed tomography (SPECT) imaging were performed on mice bearing human colorectal cancer (HT29) xenografts after injection of 99mTc-MAG3-bevacizumab.

Results Bevacizumab can be radiolabeled with 99mTc with a radiochemical yield of higher than 68% and radiochemical purity of higher than 99% under the optimized reaction conditions. VEGFA expression was measured by western blot. Biodistribution and SPECT imaging studies in HT29 tumor-bearing mice demonstrated a high and specific uptake of the radiotracer in VEGF -positive tumors. 99mTc-MAG3-bevacizumab mainly accumulated in the tumor, blood, liver, heart and lung, while very little uptake was observed in other organs, such as Intestine and spleen at 24 hours after injection.

Conclusions We have successfully synthesized 99mTc-MAG3-bevacizumab with reliable and high radiochemical yield and radiochemical purity. This tracer exhibited a high and specific uptake in VEGFA positive tumors. Thus, 99mTc-MAG3-bevacizumab may serve as a highly promising compound for VEGFA-based tumor SPECT imaging.