The objective was to investigate if some of the key molecular players associated with bladder hyper-permeability in interstitial cystitis/bladder pain syndrome (IC/BPS) could be visualized with molecularly-targeted magnetic resonance imaging (mt-MRI) in vivo. IC/BPS is a chronic, painful condition of the bladder that affects primarily women. It has been demonstrated over the past several decades that permeability plays a substantial role in IC/BPS. There are several key molecular markers that have been associated with permeability, including glycolsaminoglycan (GAG), biglycan, chondroitin sulfate, decorin, E-cadherin, keratin 20, uroplakin, vascular endothelial growth factor receptor 1 (VEGF-R1), claudin-2 and zonula occludens-1 (ZO-1). We used in vivo molecularly-targeted MRI (mt-MRI) to assess specific urothelial biomarkers (decorin, VEGF-R1, and claudin-2) associated with bladder hyper-permeability in a protamine sulfate (PS)-induced rat model. The mt-MRI probes consisted of an antibody against either VEGF-R1, decorin or claudin-2 conjugated to albumin that had also Gd-DTPA (gadolinium diethylene triamine penta acetic acid) and biotin attached. mt-MRI- and histologically-detectable levels of decorin and VEGF-R1 were both found to decrease following PS-induced bladder urothelial hyper-permeability, whereas claudin-2, was found to increase in the rat PS model. Verification of the presence of the mt-MRI probes were done by targeting the biotin moiety for each respective probe with streptavidin-hose radish peroxidase (HRP). Levels of protein expression for VEGF-R1, decorin and claudin-2 were confirmed with immunohistochemistry. In vivo molecularly-targeted MRI (mt-MRI) was found to successfully detect alterations in the expression of decorin, VEGFR1 and claudin-2 in a PS-induced rat bladder permeability model. This in vivo molecularly-targeted imaging approach has the potential to provide invaluable information to enhance our understanding of bladder urothelium hyper-permeability in IC/BPS patients, and perhaps be used to assist in developing novel therapeutic strategies.
American journal of nuclear medicine and molecular imaging. 2020 Feb 25*** epublish ***
Rheal A Towner, Nataliya Smith, Debra Saunders, Megan Lerner, Beverley Greenwood-Van Meerveld, Robert E Hurst
Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation Oklahoma, OK, USA., Department of Surgery Research Laboratory, University of Oklahoma Health Sciences Center Oklahoma, OK, USA., Department of Physiology, University of Oklahoma Health Sciences Center Oklahoma, OK, USA., Department of Urology, University of Oklahoma Health Sciences Center Oklahoma, OK, USA.