Abstract 18471: Novel Macrophage Targetable Theranostic Photoactivation Simultaneously Images Plaque Macrophages and Regresses the Atheromata
Background and Hypothesis: Macrophages are associated with destabilization of the atheroma. We aim to develop light-activatable theranostic agent targeting scavenger receptor expressed on macrophages and assess the hypothesis that it can image plaque macrophages and also reduce plaque propagation/inflammation.
Method and Results: A Chlorin e6 (Ce6) conjugated photoactivatable theranostic probe targeting scavenger receptors on macrophage was newly fabricated. In vitro, photoactivatable theranostic probe was taken up by activated macrophages and induced phototoxicity in a light dose dependent manner. 12 hours after i.v. injection of the theranostic probe (Ce6 0.5 mg/kg) in apoE knockout mice with FITC-dextran angiography (ex/em 490/525nm), carotid imaging by our customized intravital fluorescence microscope (IVFM) was able to clearly detect the plaque macrophages in vivo. Therapeutic irradiation with a 665nm diode laser (irradiation dose rate 200 mW/cm2) for 5 times, 30 seconds with 1 min interval, was performed. 2 weeks after laser irradiation, the serial intravital imaging showed a significant reduction of macrophage signals in vivo as compared to the baseline (p<0.01). Intriguingly, targeted plaque burden dramatically decreased as compared to non-treated plaques or controls (Figure) (p<0.01). FM and immunostainings corroborated the findings in vivo.
Conclusions: Photoactivatable theranostic probe targeting plaque macrophages could be a promising approach to simultaneously image and stabilize high-risk atheroma.
Author Disclosures: K. Park: None. J. Song: None. M. Lee: None. B. Yi: None. J. Kim: None. H. Kim: None. J. Jeon: None. D. Oh: None. W. Oh: None. H. Yoo: None. J. Kim: None.
- © 2016 by American Heart Association, Inc.