Abstract 15508: Development of a Small Peptide-Based Molecular Imaging Probe Targeting LOX-1 for Noninvasive Identification of Atherosclerotic Plaque
Objective: The oxidized low density lipoprotein (ox-LDL) receptor, LOX-1, mediates the initiation, progression, and destabilization of atherosclerotic plaques, and may be an ideal target for molecular imaging of vulnerable lesions. We have demonstrated that a multimodality imaging probe based on a monoclonal antibody toward LOX-1 is able to accurately detect atherosclerosis in vivo in a murine model. We aimed to develop a clinically useful peptide-based multi-modality imaging probe targeting LOX-1.
Methods: Using phage display selection techniques, we selected a peptide with high affinity, specificity, and selectivity for both mouse and human LOX-1. The lead peptide, LOX-1 binding peptide (LBP) was conjugated to a liposome designed for multimodality imaging (LBP-Lip), and tested in ApoE-/- and wild type mice. Fluorescence molecular tomography (FMT) images were obtained in vivo and ex vivo at multiple time points, and compared with aortic atherosclerotic plaque burden on Sudan IV staining.
Findings: LBP has an affinity of 9.88 +/− 0.12 nM for human rh-LOX-1, good cross-reactivity with mouse rm-LOX-1, 7.65-fold specificity for rh-LOX-1 compared to human serum, and 4.13-fold selectivity for rh-LOX-1 compared to rh-dectin, a highly homologous protein to LOX-1. LBP-lip has excellent affinity (404.9 +/− 0.1 femtoM) for rh-LOX-1. In vivo and ex vivo FMT images demonstrate that LBP-Lip colocalizes with atherosclerotic plaque on histology of ApoE-/- murine aortas, but did not bind to wild-type mouse aortas (Fig 1).
Conclusions: We have developed a LOX-1 targeted liposome allowing noninvasive detection of atherosclerosis in a mouse model, with excellent correlation to histology. LOX-1-targeted multi-modality imaging agents could potentially provide clinically useful tools for assessing plaque risk, the need for medical or invasive interventions, and for monitoring response to anti-atherosclerotic therapies.
- © 2010 by American Heart Association, Inc.