A novel method for preparing microbubbles targeting hepatocellular carcinoma.

BACKGROUND/AIMS: To develop an optimized formula for more stable and effective coupling of albumin microbubbles (MBs) to monoclonal antibodies (mAbs) using a biotin-avidin system.

METHODOLOGY

Biotin modified albumin MBs were first linked with avidin (Av) followed by treatment with biotinylated mAbs. Each step was monitored using flow cytometry, and the results were summarized with an optimized formula. A hepatocellular carcinoma (HCC) and a normal human hepatocyte cell line were used to examine the effectiveness of this novel linkage strategy.

RESULTS

The present experiments resulted in 96.05% of MBs bound to their microbubble shells. Av-Bio-MBs were conjugated to mAbs specific for the Hab18G/CD147 cell line. In vitro, CD147-specific MBs were found to bind to HCC cells, but not normal human hepatocyte cells. After exposure to Hab18G rosette-blocking mAb solution, few targeted MBs bound to HCC cells.

CONCLUSIONS

Conjugation of MBs with biotinylated mAbs forming an Av-Bio-MB system is a novel and attractive tool for HCC-targeting and molecular imaging.