Volumetric Optoacoustic Imaging Of Tumor Cell Death Using A Targeted Imaging Agent

Multispectral optoacoustic tomography (MSOT) generates high-resolution cross-sectional images in less than a second. MEDI3039, is a newly described agonist of the TNF-related apoptosis-inducing ligand receptor2 (TRAILR2), which has been shown in preclinical studies to preferentially induce cell death in cancer versus normal cells1. We show here that MSOT, when used with a near infra-red (NIR) fluorophore-labelled protein domain of Synaptotagmin-I (C2Am-750, ~15kDa) that binds to phosphatidylserine (PS) exposed by apoptotic and necrotic cells2, can be used to image MEDI3039-induced cell death within the entire tumor region. Non-specific probe retention was assessed using a site-directed mutant (iC2Am-680 or iC2Am-750).PS-specific binding of C2Am-750 to MEDI3039-treated TRAIL-sensitive Colo205 and TRAIL-resistant HT-29 human colon adenocarcinoma cells in vitro was evaluated by flow …