Using an acute mouse thrombosis
model, where the carotid artery is exposed to ferric-chloride to induce
thrombosis, thrombi were successfully visualised via MRI (von zur Muhlen
et al., 2008; Ta et al., 2011, 2017), nuclear imaging (Heidt et al.,
2011; Ardipradja et al., 2014; Hagemeyer et al., 2014), ultrasound (Wang
et al., 2012, 2014, 2016), and optical imaging (Lim et al., 2017). Upon
the injection of microparticles, iron oxide (MPIOs) coupled with
scFvanti-GPIIb/IIIa, these targeted MPIOs were shown to
bind at the site of blood clots, resulting in a decrease of signal
intensity in T2-weighted MRI (Figure 9) (von zur Muhlen et al., 2008).
The authors further demonstrated that this diminution in signal could be
reversed after the injection of urokinase as a fibrinolytic drug,
indicating successful thrombolysis (Figure 10). Similarly,
scFvanti-GPIIb/IIIa radiolabelled with Indium-111
(111In) and 18F has been used for
the imaging of activate platelets in thrombi using SPECT (Figure 11 and
Video 1) (Heidt et al., 2011) and PET (Ardipradja et al., 2014),
respectively. In another murine study, Ziegler et al. radiolabelled
scFvanti-GPIIb/IIIa with 64Cu, and
visualised the accumulation of activated platelets in ischemic and then
reperfused myocardium (Ziegler et al., 2016). This PET imaging approach
showed an uptake of radioactivity in the myocardium of mice, after just
a- 10 min period of ischemia (Figure 12).(Ziegler et al., 2016).
Noteably, after 10 min there was no increase of classical markers of
cardiac ischemia, indicating that the imaging of platelets provides a
means of detection of cardiac ischaemia with an unprecedented
sensitivity. Using ultrasound, Wang et al. demonstrated direct
and immediate visualisation of thrombi using microbubbles coupled with
scFvanti-GPIIb/IIIa (Figure 13) (Wang et al., 2012).
Realtime molecular ultrasound imaging can be used to image the success
or failure of thrombolysis (Figure 14), and importantly, the dislodgment
of a thrombus can be directly visualised (Video 2) (Wang et al., 2012).
Lim et al. conjugated near-infrared dyes onto
scFvanti-GPIIb/IIIa, which allowed early and sensitive
detection of thrombi using in vivo three-dimensional optical
imaging (Lim et al., 2017).