In vivo studies showed a significant T 1 × T 2 signal loss in the clot region of 24% after i.v. Furthermore, the control blood showed a higher value of the T 1 × T 2 signal (39% ), being the blood clots with low coagulation times the samples with the lowest values measured by MRI. MRI in vitro studies showed a sharp decrease in the T 1 × T 2 signals measured for aged clots incubated with KCREKA-NPs compared with fresh clots (47% to 26% ). In vitro studies showed that blood clots with low coagulation times were disrupted by rtPA, whereas aged clots were almost insensitive to the presence of rtPA. In the same line, r 2 relaxivities were also similar for the nanoparticles (149 ± 2 mM Fe s −1 and 151 ± 5 mM Fe s −1), whereas the r 1 relaxivity was higher for KCREKA-NPs (1.68 ± 0.29 mM Fe s −1 vs. The sizes of the nanoparticles, measured via DLS, were similar for both KCREKA-NPs and PEG-NPs (23 ± 4 nm, PDI = 0.11 and 25 ± 8 nm, PDI = 0.24, respectively). KCREKA-NPs were synthesized by attaching the peptide to the amino (N) termini of the PEG-NPs. Magnetic resonance imaging (MRI) of blood clots was performed in vitro and in vivo in animal models of thromboembolic stroke. Gd-labeled KCREKA peptides were synthesized and attached onto the surface of PEGylated superparamagnetic nanoparticles. In this work, we describe the synthesis and the in vitro characterization of a new diagnostic nanoparticle, as well as the in vivo evaluation in an animal model of thromboembolic stroke. Current imaging methods can successfully identify occlusions in large vessels however, there is still a need for contrast agents capable of visualizing small thrombi in ischemic stroke patients. In addition, fibrin content also influences the efficacy of mechanical thrombectomy. Fibrin is one of the main components of blood clots causing ischemic stroke and is the target of rtPA upon activation of plasminogen in the clot.
Recanalization of the occluded artery is the gold standard treatment for acute ischemic stroke, which includes enzymatic fibrinolytic treatment with the use of recombinant tissue plasminogen activators (rtPAs) to disrupt the occluding clot, the use of mechanical thrombectomy to physically remove the clot, or a combination of both.
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