Gadolinium-bearing red cells as blood pool MRI contrast agents

Abstract

Human and rat red blood cells (RBCs) were loaded with gadolinium DTPA dimeglumine using an osmotic pulse technique to create a blood pool contrast agent for MRI. The resulting packed red cells contained 30.9 +/- 3.3 (1 SD) mmol Gd/liter for humans and 24.7 +/- 3.5 (1 SD) mmol Gd/liter for rats. Longitudinal relaxation rate constant of human RBCs increased from 2.0 +/- 0.1 to 145.6 +/- 36.2 s(-1); the transverse relaxation rate constant increased from 6.8 +/- 1.2 to 562 +/- 410 s(-1). For rat RBCs, R1 increased from 1.45 +/- 0.15 to 84.8 +/- 23.9 s(-1); R2 increased from 7.1 +/- 0.64 to 247 +/- 158 s(-1). Affinity for oxygen was slightly reduced (control P50 = 22.3 +/- 2.3 versus experimental P50 = 27.3 +/- 1.3, P < 0.01), as was mechanical deformability. No drop in relaxivities was seen after 5 days of storage. The apparent volume of distribution was 0.0164 +/- 0.003 liter/kg, biologic half-life 4.38 +/- 0.34 h, and total plasma clearance 0.003 +/- 0.0006 liter/kg/h. Compared with Gd-DTPA "free" in the plasma, tissue enhancement from RBCs was initially lower but was much prolonged. Preparation is simple enough to be reproduced by most laboratories.