CENTRAL ILLUSTRATION. Molecular Imaging of Phospholipid Asymmetry During Apoptosis.

The phospholipids in the cell membrane lipid bilayer are asymmetrically distributed with phosphatidylserine (PS) and phosphatidylethanolamine (PE) in the inner tab and phosphatidylcholine (PC) and sphingomyelin (SM) on the outer. This asymmetric distribution of phospholipids across the membrane bilayer is maintained by enzymes such as translocase and flippase. During apoptotic cell death, as a result of enzymatic alteration, normal phospholipid asymmetry within the cell membrane is lost, resulting in exteriorization of PS and PE. Activation of scrambalase exaggerates the random distribution. The exposure of PS acts as an “eat-me signal” for macrophages to have the apoptotic bodies removed. An endogenous protein, annexin-V possesses nanomolar affinity for externalized PS. Radiolabeled annexin-V has previously been used for noninvasive imaging of apoptotic cell death. Although effective for apoptosis imaging, annexin-V shows substantial off-target organ radiation burden. Like PS, apoptotic cell membranes also express PE. Even in larger quantities, PE can be targeted by an antibiotic-duramycin radiolabeled with technetium-99m. The current study compares the 2 probes targeted at the altered cell membranes. The study not only demonstrates the efficacy of imaging with duramycin but also its favorable off-target organ profile.