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Original Article Fluorescence Tomography of Rapamycin-Induced Autophagy and Cardioprotection In Vivo Howard H. Chen, PhD; Choukri Mekkaoui, PhD; Hoonsung Cho, PhD; Soeun Ngoy, BS; Brett Marinelli, BS; Peter Waterman, BS; Matthias Nahrendorf, MD, PhD; Ronglih Liao, PhD; Lee Josephson, PhD; David E. Sosnovik, MD Background—Autophagy is a biological process during which cells digest organelles in their cytoplasm and recycle the constituents. The impact of autophagy in the heart, however, remains unclear in part because of the inability to noninvasively image this process in living animals. Methods and Results—Here, we report the use of fluorescence molecular tomography and a cathepsin-activatable fluorochrome to image autophagy in the heart in vivo after ischemia/reperfusion and rapamycin (RAP) therapy. We show that cathepsin-B activity in the lysosome is upregulated by RAP and that this allows the expanded lysosomal compartment in autophagy to be imaged in vivo with fluorescence molecular tomography. We further demonstrate that the delivery of diagnostic nanoparticles to the lysosome by endocytosis is enhanced during autophagy. The upregulation of autophagy by RAP was associated with a 23% reduction (P<0.05) of apoptosis in the area at risk and a 45% reduction in final infarct size (19.6±5.6% of area at risk with RAP versus
Circulation: Cardiovascular Imaging – Wolters Kluwer Health
Published: May 1, 2013
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