In Vivo Molecular Imaging of Thrombosis and Thrombolysis Using a Fibrin-binding Positron Emission Tomography Probe
Background—Fibrin is a major component of arterial and venous thrombi and represents an ideal candidate for molecular imaging of thrombosis. Here, we describe imaging properties and target uptake of a new fibrin-specific PET probe for thrombus detection and therapy monitoring in two rat thrombosis models.
Methods and Results—The fibrin-binding probe FBP7 was synthesized by conjugation of a known short cyclic peptide to a cross-bridged chelator (CB-TE2A), followed by labeling with copper-64. Adult male Wistar rats (n=26) underwent either carotid crush injury (mural thrombosis model) or embolic stroke (occlusive thrombosis model) followed by rtPA treatment (10 mg/kg, i.v.). FBP7 detected thrombus location in both animal models with a high PET target-to-background ratio that increased over time (>5-fold at 30-90 min, >15-fold at 240-285 min). In the carotid crush injury animals, biodistribution analysis confirmed high probe uptake in the thrombotic artery (~0.5 %ID/g; >5-fold greater than blood and other tissues of the head and thorax). Similar results were obtained from ex vivo autoradiography of the ipsilateral vs. contralateral carotid arteries. In embolic stroke animals, PET-CT imaging localized the clot in the internal carotid/middle cerebral artery segment of all rats. Time-dependent reduction of activity at the level of the thrombus was detected in rtPA-treated rats but not in vehicle-injected animals. Brain autoradiography confirmed clot dissolution in rtPA-treated animals, but enduring high thrombus activity in control rats.
Conclusions—We demonstrated that FBP7 is suitable for molecular imaging of thrombosis and thrombolysis in vivo, and represents a very promising candidate for bench-to-bedside translation.
- Received December 11, 2013.
- Accepted April 24, 2014.