Surfactant-Stripped Micelles for NIR-II Photoacoustic Imaging through 12 cm of Breast Tissue and Whole Human Breasts

Abstract

Surfactant-stripped micelles are formed from a commercially available cyanine fluoroalkylphosphate (CyFaP) salt dye and used for high contrast photoacoustic imaging (PAI) in the second near-infrared window (NIR-II). The co-loading of Coenzyme Q10 into surfactant-stripped CyFaP (ss-CyFaP) micelles improves yield, storage stability, and results in a peak absorption wavelength in the NIR-II window close to the 1064 nm output of Nd-YAG lasers used for PAI. Aqueous ss-CyFaP dispersions exhibit intense NIR-II optical absorption, calculated to be greater than 500 at 1064 nm. ss-CyFaP is detected through 12 cm of chicken breast tissue with PAI. In preclinical animal models, ss-CyFaP is visualized in draining lymph nodes of rats through 3.1 cm of overlaid chicken breast tissue. Following intravenous administration, ss-CyFaP accumulates in neoplastic tissues of mice and rats bearing orthotopic mammary tumors without observation of acute toxic side effects. ss-CyFaP is imaged through whole compressed human breasts in three female volunteers at depths of 2.6-5.1 cm. Taken together, these data show that ss-CyFaP is an accessible contrast agent for deep tissue PAI in the NIR-II window.