A New Class of Smart Gadolinium Contrast Agent for Tissue pH Probing Using Magnetic Resonance Imaging

Abstract

Detecting tissue pH in vivo is extremely vital for medical diagnosis and formulation of treatment decisions. To this end, many investigations have been carried out to develop an accurate and efficient method of in vivo pH measurement. Most of the techniques developed so far suffer from inadequate accuracy, due to poor sensitivity at low concentration of the target or nonspecific interactions within the tissue matrix. To overcome these issues, we describe herein the development of a simple, yet reliable, way to estimate pH with high precision using a Gd(III)-DOTA-silyl-based acid-labile group as a pH-sensitive contrast agent with Magnetic Resonance Imaging (MRI). With this method, a change in T 1 weighted image intensity of the newly developed pH-sensitive contrast is directly linked to the proton concentration in the media. As a result, we were able estimate the pH of the target with 95% reliability.

Ratiometric chemical exchange saturation transfer pH mapping using two iodinated agents with nonequivalent amide protons and a single low saturation power

“…The perturbation of kidney pH is also often associated with pathologically changed renal physiology (6,7). Therefore, noninvasive imaging methods for absolute pH measurement have potential utility for disease diagnoses and evaluating responses to pH-dependent therapies (8)(9)(10)(11)(12), such as using sodium bicarbonate to alkalinize the tumor microenvironment (13).…”