Targeted Contrast Agents for Magnetic Resonance Imaging: Possibilities and Limitations

Introduction: Active targeting of contrast agents for magnetic resonance imaiinghas been &died by several investigators over the last years (1,2). The methods used include targeting via antibodies and receptors. Most of these studies have however been performed at non-clinical high field-strengths using highresolution imaging in anesthetised animals. The ability to detect the contrast enhancing effect on the targeted tissue depends on both the Tl relaxivity of the agent at the target site and on the concentration of contrast agent within a given voxel. For intravascular targets, e.g. clots, the concentration of bound material is likely to be the limiting factor due to limited penetration of the contrast agent beyond the surface of the clot. The purpose of this study was therefore to investigate the use of a targeted contrast agent for magnetic resonance imaging in clot models and to study the feasibility of such an agent in a clinical setting. Material and Methods: A USPIO particle was prepared with a RGD peptide (3) to target the integrin aI& (4) which is expressed when blood-clots are formed. Imaging was performed using a 1 ST clinical imaging system (Gyroscan ACS-NT, Philips Medical Systems) using a spoiled 3D-gradient echo acquisition. Ex viva model: a clot was formed around a glass core Tom whole human blood and inserted in a test tube containing heparinized blood spiked with the contrast agent. The test tube was then gently rotated for two hours and washed before imaging was performed. Comparison was made using the USPIO without the targeting vector. Imaging was performed with the following resolutions: 0.3 1x0.3 1, 0.62x0.62 and 1.25x1.25 mm’ using an 80 mm surface coil. In viva model: clots were induced in the jugular veins of pigs using a previously described technique (5). Imaging was performed 5 hours post administration of 4 mg Fe/kg of the targeted agent using a 22 mm surface coil. At this time point the background signal from blood was down to baseline values. The resolutions used for the in viva experiment were 0.125x0.125, 0.195x0.195 and 0.585x0.585 mm’. In both models, signal intensity profiles were drawn over the enhanced area and the difference between baseline and peak signal intensity was measured. Results: In the ex viva model, targeted USPIO gave a signal enhancement over the non-targeted USPIO of 128% at the rim of the clot in the high resolution scan. The results with the targeted USPIO are summarised in Figures 1 and 2 and Table 1. Conclusion: It is concluded that positive signal enhancement can be detected by active targeting of nanoparticles with a RGD peptide that binds to blood clots. Figure 1