Bioconjugated gold nanoparticles as a molecular based contrast agent: implications for imaging of deep tumors using optoacoustic tomography

Abstract

Purpose: Optoacoustic tomography (OAT) is a novel medical imaging method that uses optical illumination and ultrasonic detection to produce deep tissue images based on their light absorption. Abnormal angiogenesis in advanced tumors, that increases the blood content of the tumor, is an endogenous contrast agent for OAT. In early stages, however, angiogenesis is not sufficient to differentiate a tumor from normal tissue; justifying the application of an exogenous contrast agent. We have developed a molecular based contrast agent composed of gold nanoparticles conjugated to a monoclonal antibody that improves OAT imaging to potentiate its use in imaging deep tumors in early stages of cancer or metastatic lesions.

Procedure: Due to their strong optoacoustic signal, we used gold nanoparticles (NPs) as a contrast agent. To target NPs to breast cancer cells, we conjugated NPs to a monoclonal antibody that specifically binds cell surface receptors known to be overexpressed in human breast tumors.

Results: In a series of in vitro experiments, Herceptin (monoclonal antibody that binds HER2/neu) conjugated to 40 nm NPs (Mab/NPs) selectively targeted human SK-BR-3 breast cancer cells. The breast cancer cells were detected and imaged by OAT in a gelatin phantom that optically resembled breast tissue. Sensitivity experiments showed that a concentration as low as 10(9) NPs per ml were detectable at a depth of 6 cm.

Conclusion: Experimental data together with theoretical analysis demonstrate the feasibility of detection of deeply seeded small tumors that express tumor associated antigens using targeted gold NPs and OAT.