Preparation of (99m)Tc carbonyl DTPA-bevacizumab and its bioevaluation in a melanoma model.

Abstract

The objective of this study was to explore the potential of (99m)Tc carbonyl labeled DTPA-bevacizumab as a tumor imaging agent. Bevacizumab (Avastin) is a humanized monoclonal antibody (MoAb) that inhibits the vascular endothelial growth factor (VEGF). Bevacizumab was conjugated with paraisothiocyanatobenzyl diethylenetriamine pentaacetic acid (p-SCN-Bn-DTPA) and subsequently radiolabeled with (99m)Tc via the (99m)Tc carbonyl synthon. The radioconjugate after purification was characterized by SE-HPLC and its in vitro stability was determined by histidine challenge experiments. Biodistribution studies to determine the uptake by tumors were carried out in melanoma model. The radiochemical purity of (99m)Tc carbonyl labeled antibody was >98%. The radiolabeled antibody exhibited good stability in the histidine challenge experiments up to 24h when stored at 37°C. Biodistribution studies in mice bearing melanoma showed significant tumor uptake (6.9±2.2%ID/g at 24h p.i.) which was reduced to 1.6±0.4%ID/g on co-injection with cold Bevacizumab. The (99m)Tc carbonyl-DTPA-bevacizumab conjugate with good radiochemical purity, excellent stability and good specificity for VEGF indicates its potential as a radioimmunoscintigraphy agent for various cancers.