Quantitative imaging of gene therapy delivery vehicles using CEST-NMR/MRI

Abstract

We hypothesized that AAV2 capsids may generate endogenous CEST contrast similar to LRP. We tested this using NMR CEST under varying pH, density, biological transduction stage, across serotypes and mixed biological media. Subsequent experiments determined the pH-dependent exchange rate and optimized CEST saturation schemes for AAV contrast detection at 7T. The results of this study reveal that AAV capsids generate endogenous CEST contrast around 0.6-0.8ppm. Exchangeable protons are likely from serine and threonine residues on the AAV capsid. Based on calculated fast exchange rates, an optimized CEST saturation scheme generated robust CEST contrast in mixed biological media phantoms at 7T.