Age-related blood half-life of particulate contrast material: experimental results with a USPIO in rats

It has been well established in the literature that phagocytic activity in animals and humans changes with age, but this phenomenon has not yet been investigated for particulate contrast agents. The present study was therefore performed to determine the effect of age on blood half-life of a superparamagnetic iron oxide blood pool contrast agent and on the velocity of its uptake in the liver and spleen of the rat by means of magnetic resonance (MR) imaging. A total of 18 rats (group A: 214-255 g, age: 45-50 days; group B: 432-563 g, age: 100-120 days) were imaged at 1.5 T using a 3D gradient-recalled echo (GRE) sequence (TR/TE 6.6/2.3 msec; alpha 25 degrees, frontal). Images were acquired before and every 3-5 minutes for up to 30 minutes after i.v. injection of 30 micromol Fe/kg of a citrate-coated superparamagnetic iron oxide-based contrast agent (VSOP-C43). Intravenous injection of VSOP-C43 resulted in a pronounced initial signal enhancement in vessels, which decreased with a half-life of 8.4 +/- 0.9 minutes in group A and of 15.9 +/- 2. 4 minutes in group B (P < 0.01). The half-life of signal decrease was 11.6 +/- 2 minutes and 19.9 +/- 4.4 minutes in the liver (P < 0. 01) and 19.6 +/- 3.1 minutes and 26.7 +/- 5.2 minutes in the spleen (not significant). The results show that the age-related phagocytic activity has a significant effect on the circulation time and velocity of uptake of a particulate MR imaging contrast agent. This fact must be taken into consideration in both the preclinical and clinical development of particulate contrast material and in the clinical application of such agents.