In vivo photoacoustic imaging of cancer using indocyanine green-labeled monoclonal antibody targeting the epidermal growth factor receptor

Abstract

Photoacoustic (PA) imaging is an attractive imaging modality for sensitive and depth imaging of biomolecules with high resolution in vivo. The aim of this study was to evaluate the effectiveness of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (panitumumab; Pan) labeled with indocyanine green derivative (ICG-EG4-Sulfo-OSu), Pan-EG4-ICG, as a PA imaging probe to target cancer-associated EGFR. In vitro PA imaging studies demonstrated that Pan-EG4-ICG yielded high EGFR-specific PA signals in EGFR-positive cells. To determine the optimal injection dose and scan timing, we investigated the biodistribution of radiolabeled Pan-EG4-ICG (200–400 μg) in A431 tumor (EGFR++)-bearing mice. The highest tumor accumulation (29.4% injected dose/g) and high tumor-to-blood ratio (2.1) was observed 7 days after injection of Pan-EG4-ICG (400 μg). In in vivo PA imaging studies using Pan-EG4-ICG (400 μg), the increase in PA signal (114%) was observed in A431 tumors inoculated in the mammary glands 7 days post-injection. Co-injection of excess Pan resulted in a 35% inhibition of this PA signal, indicating the EGFR-specific accumulation. In conclusion, the ICG-labeled monoclonal antibody (i.e., panitumumab) has the potential to enhance target-specific PA signal, leading to the discrimination of aggressiveness and metastatic potential of tumors and the selection of effective therapeutic strategies.