Perturbations of renal and systemic pH accompany diseases of the kidney, such as renal tubular acidosis, and the ability to image tissue pH would be helpful to assess the extent and severity of such conditions. A dual-contrast-agent strategy using two gadolinium agents, the pH-insensitive GdDOTP(5-) and the pH-sensitive GdDOTA-4AmP(5-), has been developed to generate pH maps by MRI. The renal pharmacokinetics of the structurally dissimilar pH-insensitive contrast agents GdDTPA(2-) and GdDOTP(5-) were found to be similar. On that basis, and on the basis of similarity of structure and charge, the renal pharmacokinetics of GdDOTP(5-) and GdDOTA-4AmP(5-) were assumed to be identical. Dynamic T(1)-weighted images of mice were acquired for 1 hr each following boluses of GdDOTP(5-) and GdDOTA-4AmP(5-). The time-varying apparent concentration of GdDOTP(5-) and the time-varying enhancement in longitudinal relaxation rate following GdDOTA-4AmP(5-) were calculated for each pixel and used to compute pH images of the kidneys and surrounding tissues. MRI pH maps of control mice show acidic regions corresponding to the renal papilla, calyx, and ureter. Pretreatment of mice with the carbonic anhydrase inhibitor acetazolamide resulted in systemic metabolic acidosis and accompanying urine alkalinization that was readily detected by this dual-contrast-agent approach.
Copyright 2003 Wiley-Liss, Inc.