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Targeted Contrast Agents

Mirko Meißner und Daniel Dürschmied

Our investigations are concentrated on finding suitable contrast agents which can be targeted to activated platelets. In addition to fluorinated contrast agents we are studying agents based on Gadolinium as well as agents based on iron oxide particles. In a current study we investigate the feasibility of detecting coronary artery thrombosis by molecular MRI using micrometer sized particles of iron oxide (MPIO) conjugated to a single chain antibody targeting ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa, hereafter referred to as LIBS-MPIO contrast agent.

The left anterior descending coronary artery (LAD) was exposed by lateral thoracotomy and incubated with ferric chloride to induce non-occlusive thrombosis in intubated male C57Bl/6 mice. Either LIBS-MPIO oder control-MPIO (with control antibody) was injected intravenously.

Figure 1.
For MRI, hearts were fixed in 4% paraformaldehyde for at least 12 h, then perfused with 1.5 mM Gadolinium and placed in 100% FC84. Scans were performed on a 9.4 T system with a three dimensional high resolution gradient echo sequence (3D-FLASH). MRI revealed intact anatomy of fixed hearts (here with control MPIO) with left (LV) and right (RV) ventricular cavum, aortic valve (A) and left anterior descending artery (LAD). Sutures for fixation of the filter paper left intramyocardial defects (*).

 Figure 2.
The proximal and medial part of the LAD after injection of control- (left) or LIBS-MPIOs (right) in hearts from different mice. Severe hypointense regions along the LAD could only be detected in hearts from animals injected with LIBS-MPIO. Furthermore histological investigations confirmed both, the presence of a thrombus and the binding of MPIOs in the LAD region which was hypointense in MRI. These findings suggest that molecular MRI with LIBS-MPIOs allows the detection of coronary artery thrombosis in mice ex vivo.

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