263 - In vivo detection of bladder permeability biomarkers in rodent models using molecular-targeted MRI

Abstract

Bladder permeability is associated with interstitial cystitis (IC). We previously used contrast-enhanced MRI to assess bladder permeability in a protamine sulfate (PS)-bladder permeability induced rat model, as well as in human patients for IC. This study focuses on the use of molecular-targeted MRI (mtMRI) to assess bladder permeability biomarkers in vivo in rodent bladder permeability models. Decorin, VEGFR1 (vascular endothelial growth factor receptor 1), and claudin-2 are all known bladder urothelium markers. Rats (treated with PS)/mice (URO-MCP-1 transgenic treated with lipopolysaccharide (LPS)) were anesthetized with isoflurane for either intravesical PS/LPS or saline administration, and for MRI scans. Targeted contrast agent probes for claudin-2, VEGFR1 or decorin were used to obtain bladder permeability biomarker specific images. Multiple bladder region MR image slices were taken. Pixel-by-pixel relaxation maps were reconstructed from a series of T1-weighted images using a nonlinear two-parameter fitting procedure. The T1 value of a specified region-of-interest (ROI) was computed from all the pixels in the identified ROIs. mtMRI was able to demonstrate altered levels of claudin-2 (Rat PS and URO-MCP-1 mouse LPS models), VEGFR1 and decorin in PS-induced permeable rat bladders, compared to saline-treated controls. Data indicates the feasibility of conducting in vivo mtMR imaging for the bladder permeability biomarker claudin-2 in PS-exposed rat bladders. Claudin-2 levels are significantly increased (p