Repositioning Clofazimine as a Macrophage-Targeting Photoacoustic Contrast Agent.

ABSTRACT: Photoacoustic Tomography (PAT) is a deep-tissue imaging modality, with potential clinical applications in the diagnosis of arthritis, cancer and other disease conditions. Here, we identified Clofazimine (CFZ), a red-pigmented dye and anti-inflammatory FDA-approved drug, as a macrophage-targeting photoacoustic (PA) imaging agent. Spectroscopic experiments revealed that CFZ and its various protonated forms yielded optimal PAT signals at wavelengths -450 to 540?nm. CFZ's macrophage-targeting chemical and structural forms were detected with PA microscopy at a high contrast-to-noise ratio (CNR?>?22?dB) as well as with macroscopic imaging using synthetic gelatin phantoms. In vivo, natural and synthetic CFZ formulations also demonstrated significant anti-inflammatory activity. Finally, the injection of CFZ was monitored via a real-time ultrasound-photoacoustic (US-PA) dual imaging system in a live animal and clinically relevant human hand model. These results demonstrate an anti-inflammatory drug repurposing strategy, while identifying a new PA contrast agent with potential applications in the diagnosis and treatment of arthritis.

SUBMITTER: Keswani RK 

PROVIDER: S-EPMC4802322 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature