Abstract 5788: VCAM-1 Targeted PET-CT Detects Inflammatory Atherosclerotic Plaques

Abstract

Hybrid PET-CT imaging of VCAM-1 expression and vascular anatomy may facilitate simultaneous assessment of atherosclerotic lesion biology and morphology, and enhance risk assessment in individual patients. We used combined in vitro/in vivo screening of candidate affinity ligands and developed a PET reporter for imaging VCAM-1 expression with high sensitivity, specificity and translational potential. Three different phage display-derived VCAM-1 affinity peptides were tested using immobilized VCAM-1, VCAM-1 expressing cells and apoE−/− mice. A compound with a linear peptide and arborising tetrameric design showed high affinity (86.6 nM) and specificity for VCAM-1 (97% inhibition with soluble VCAM-1). This lead compound was derivatized with 18Fluorine to synthesize the clinically viable PET agent 18F-4V. In vivo PET-CT imaging showed robust uptake of 18F-4V in plaque laden arterial sections from 8 apoE−/− mice, significantly higher than in 4 wild type mice and attenuated by atorvastatin treatment (p<0.05). 18F-4V uptake was confirmed in excised aortas, colocalized with atherosclerotic plaques delineated by Oil Red O staining and correlated with mRNA levels of VCAM-1 measured by quantitative RT-PCR (R2=0.62, p=0.03). 18F-4V allows noninvasive PET-CT imaging of VCAM-1 in atheromata, has sufficient dynamic range to quantify treatment effects, and correlates with inflammatory gene expression. This approach lends itself to seamless translation to human PET-CT imaging.