Intravascular Targeted Photoactivation Guided by Optical Coherence Tomography-Near Infrared Fluorescence (OCT-NIRF) Imaging Promotes Stabilization of Atherosclerotic Plaques

Introduction and Hypothesis: Photoactivation has emerged as an innovative therapeutic strategy for coronary high-risk plaque without metallic remnants, however, limited targetable ability of photoactivator and lack of imaging guidance hinders its application to clinics. To solve these unmet needs, we developed intravascular photoactivation strategy guided by dual-modal OCT-NIRF structural-molecular imaging using a novel theranostic NIRF-emitting photoactivator. Methods and Results: Photoactivatable NIRF-emitting theranostic agent targeting scavenger receptors on macrophages was newly synthesized. The intravascular photoactivation system based on fiber type cylindrical diffuser was newly fabricated for the therapeutic light delivery to the plaques. Forty-eight hours after intravenous injection of scale-up NIRF-emitting photoactivator (equivalent Ce6 dose of 2 mg/kg), OCT-NIRF imaging was able to exactly identify the highly inflamed targets in OCT-delineated plaques of rabbit arteries. Two weeks after therapeutic light irradiation through the catheter to the NIRF enhanced macrophages, the inflammatory NIRF signals of targeted atheroma markedly decreased as compared to the controls (Figure). By comprehensive immunofluorescence analysis, photoactivation produced a prominent increase in macrophage-associated apoptotic bodies and also induced autophagy with an enhanced efferocytosis, resulting in stabilization of the atheroma. Conclusions: Intravascular photoactivation using targeted NIRF emitting photosensitizer could stabilize the inflamed plaque under the guidance of OCT-NIRF imaging. This imaging guided therapeutic innovation will be a promising theranostic strategy for the high-risk coronary plaques.