Comparison of Different Types of Blood Pool Agents (P792, MS325, USPIO) in a Rabbit MR Angiography-like Protocol

Abstract

The objective of this study is to determine the influence of the pharmacokinetic behaviors of different classes of blood pool agents (BPA) on a rabbit experimental model that mimics a magnetic resonance angiographic protocol. BPA were as follows: P792, a macromolecular agent (RCBPA), USPIO, an ultrasmall superparamagnetic iron oxide particle agent (SCBPA), and MS-325, a small gadolinium chelate that expresses intravascular behavior by reversible albumin binding. The 2 main phases of early distribution following contrast agent injection, that is, the bolus phase and the steady-state phase, are investigated by measuring Gd or Fe blood concentrations in the first 5 minutes postinjection. T1 relaxation times and r1 relaxivity were calculated at each time point of blood sampling. Furthermore, in the case of MS-325, the concentrations of the free and bound forms were calculated, according to the measured concentrations and the apparent r1 relaxivities. Injected under similar conditions, the 3 BPA have, during the bolus phase, a comparable profile to Gd-DOTA. Signal enhancement was maximum during this short bolus phase, as were the T1 relaxation times under 30 ms for all agents. At 1 minute postinjection, P792 (r1 = 39 seconds(-1) x mmol/L(-1), 20 MHz) demonstrated the same pharmacokinetic behavior as USPIO (r1 = 33 seconds(-1) x mmol/L(-1), 20 MHz): C1 minute/C0 values were 91 +/- 6% and 92 +/- 12%, respectively. Immediately after the injection at clinical dose, 74% of MS-325 was in free form, resulting in an apparent r1 relaxivity of only 13 seconds(-1) x mmol/L(-1) (20 MHz); 1 minute postinjection, the C1 minute/C0 value of 61 +/- 4% was the lowest as compared with P792 and USPIO and the bound form represented 75% of the MS-325 molecules. The BPA P792 and USPIO have favorable properties that result from their intravascular retention and their lack of extravasation, allowing optimal contrast between the vessel and the adjacent tissue for several minutes postinjection. Combining a rapid body clearance and a marked T1 effect, P792 presents optimal blood pool characteristics for angiographic applications. During the bolus phase, MS-325 is mainly in free form, which presents the disadvantage of increasing the tissue signal background, due to extravasation of the free form.