Spectroscopic photoacoustic (sPA) molecular imaging has high potential for identification of exogenous contrast agents targeted to specific markers. Antibody-dye conjugates have recently been used extensively for preclinical sPA and other optical imaging modalities for highly specific molecular imaging of breast cancer. However, antibody-based agents suffer from long circulation times that limit image specificity. Here, the efficacy of a small protein scaffold, the affibody (ABY), conjugated to indocyanine green (ICG), a near-infrared fluorescence dye, as a targeted molecular imaging probe is demonstrated. In particular, B7-H3 (CD276), a cellular receptor expressed in breast cancer, was imaged via sPA and fluorescence molecular imaging to differentiate invasive tumors from normal glands in mice. Administration of ICG conjugated to an ABY specific to B7-H3 (ABYB7-H3-ICG) showed significantly higher signal in mammary tumors compared to normal glands of mice. ABYB7-H3-ICG is a compelling scaffold for molecular sPA imaging for breast cancer detection.
Bibliographical noteFunding Information:
The authors would like to acknowledge Dr. Juergen K. Willmann for his mentorship. We acknowledge Kenneth Lau from the Proteomics Resource Facility in the Canary Center for Cancer Early Detection at Stanford for performing the mass spectrometry analysis. This study was supported by American Cancer Society 130418-RSG-17-110-01-TBG (BJH), NIH R21EB022214 (KEW), and NIH K99EB023279 (KEW). The Stanford Neuroscience Microscopy Service was supported by NIH NS069375. The Vevo LAZR was upgraded under grant NIH 1-S10-OD01034401.