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Sci Rep. 2016 Mar 22;6:23528. doi: 10.1038/srep23528.

Repositioning Clofazimine as a Macrophage-Targeting Photoacoustic Contrast Agent.

Author information

1
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109.
2
Department of Radiology, University of Michigan, Ann Arbor, MI 48109.
3
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109.
4
National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD 20850.

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.

PMID:
27000434
PMCID:
PMC4802322
DOI:
10.1038/srep23528
[Indexed for MEDLINE]
Free PMC Article

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