In vivo cellular-level real-time pharmacokinetic imaging of free-form and liposomal indocyanine green in liver

Abstract

Indocyanine green (ICG) is a near-infrared fluorophore approved for human use which has been widely used for various clinical applications. Despite the well-established clinical usage, our understanding about the microscopic <i>in vivo</i> pharmacokinetics of systemically administered ICG has been relatively limited. In this work, we successfully visualized real-time <i>in vivo</i> pharmacokinetic dynamics of the intravenously injected free-form and liposomal ICG in cellular resolution by utilizing a custom-built video-rate near infrared laser-scanning confocal microscopy system. Initial perfusion and clearance from blood stream, diffusion into perisinusoidal space, and subsequent absorption into hepatocyte were directly visualized <i>in vivo</i>. The quantification analysis utilizing the real-time image sequences revealed distinct dynamic <i>in vivo</i> pharmacokinetic behavior of free-form and liposomal ICG.