title: 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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Rahul K
authors.initials: RK
authors.lastname: Keswani
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI 48109.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Chao
authors.initials: C
authors.lastname: Tian
authors.affiliation: National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD 20850.
authors.forename: Tyler
authors.initials: T
authors.lastname: Peryea
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Gandikota
authors.initials: G
authors.lastname: Girish
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI 48109.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Xueding
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Gus R
authors.initials: GR
authors.lastname: Rosania
mesh_terms: D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002991:Clofazimine / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D061088:Photoacoustic Techniques / Q000379:methods*
chemical_list: D000893:Anti-Inflammatory Agents; D002991:Clofazimine