Dual‐modality imaging for identifying thrombosis via platelet GPIIb/IIIa receptor targeted cyclic RGDfK microbubbles

Autor: Wang, Yabin, Zhang, Yang, Yang, Ning, Zhang, Xiaoting, Ma, Sai, Xu, Mengqi, Xu, Yunxue, Gao, Shan, Fang, Yan, Li, Na, Li, Sulei, Liang, Ping, Zhang, Xu, Fan, Li, Cao, Feng
Zdroj: iRADIOLOGY; June 2024, Vol. 2 Issue: 3 p227-239, 13p
Abstrakt: Acute thrombotic events play a major role in various cardiovascular diseases. Therefore, direct thrombus imaging can be proved beneficial for early diagnosis and prompt therapy of thrombosis. Our study investigated targeted dual‐modality cyclic arginine‐glycine‐aspartic micro bubbles (cRGD‐MBs) for direct imaging of thrombi by fluorescence and ultrasound. cRGD‐MBs were prepared by mechanical vibration and chemical chelation methods. Coulter counter analysis demonstrated that the cRGD‐MBs were well dispersed, with diameters ranging from 1 to 3 μm. They emitted bright red fluorescence under an excitation wavelength of 660 nm. In vivo fluorescence and ultrasound imaging revealed that cRGD‐MBs accumulated at the site of thrombus in the carotid artery with significant fluorescence and ultrasonic signal. This study showed that novel microbubble cRGD‐MBs were successfully synthesized, and that these could potentially be used as contrast agents for immediate diagnosis of acute thrombus in vivo. Ultrasound and fluorescence imaging of cRGD‐MBs in mice in situ thrombotic model. Cyclopeptide cRGDfK‐targeted microbubbles (cRGD‐MBs) were conjugated with DSPC, DSPE‐PEG‐cRGDfk, and DiD by thin‐film dispersion and self‐assembly method. Mice in situ thrombotic model was constructed using FeCl3‐soaked filter paper on the exposed left common carotid artery (CCA) for 5 min. Fluorescence imaging showed that it could obtain significantly higher fluorecence signal intensity at the lesion of left CCA after cRGD‐MBs intravascular injection in the mice in situ thrombotic model group compared with that in thrombus + tirofiban pretreated group. In vivo ultrasound imaging revealed that whether in B‐mode or contrast‐mode, the increase of gray value in situthrombotic model injected with cRGD‐MBs was notably higher than that in the thrombus + tirofiban pretreated group. Immunofluorescence staining of CCA tissues confirmed that clear green fluorescence signal of FITC‐labeled CD62p antibody at the thrombus was well co‐located with the red fluorescence signal of cRGD‐MBs. All these suggest that cRGD‐MBs, which have high affinity for the activated GPIIb/IIIa receptor on platelets, can serve as a novel ultrasonic/fluorescence contrast agent for effectively monitoring thrombus in vivo.
Databáze: Supplemental Index