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/cm 2 ) 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 Conclusions: Photoactivatable theranostic probe targeting plaque macrophages could be a promising approach to simultaneously image and stabilize high-risk atheroma.