Abstract 335: M.R Imaging of an Arachidonic Acid Induced Mouse Model of Thrombosis Using an Activated Platelets Targeted Paramagnetic Contrast Agent
Activated platelets play a critical role in thrombogenesis. Imaging activated platelets may therefore represent a unique opportunity to identify thrombi and characterize vulnerable/high-risk atherosclerotic plaques. We used a model mimicking inflammatory thrombosis via topical application of arachidonic acid (AA) on the carotid artery and imaged thrombi formation using an activated platelet targeted MRI contrast agent (P975) composed of a peptide targeting the glycoprotein GPIIb/IIIa conjugated to Gd-DOTA. After in vitro specificity of P975 to activated human platelets was demonstrated, 17 wild type mice were used for in vivo experiments. The right carotid was surgically isolated and thrombosis was induced by applying 4 μl of AA for 1 minute (200 mg/ml). MRI at 9.4T was performed at baseline and longitudinally over 2 hours after P975 or Gd-DOTA injection (both groups: 100 μmol Gd/kg, N=5). In vivo specificity of P975 to activated platelets was demonstrated by using a GPIIb/IIIa antagonist (Eptifibatide) prior to P975 injection (N=5). The contralateral carotid (N=5) and a sham surgery group (N=2) where EtOH was topically applied were used as controls. P975 showed a good affinity for activated platelets with an IC50 value of 2.6 μM. In animals with thrombosis, P975 produced an immediate and sustained increase in ΔCNR values whereas Gd-DOTA only displayed an early enhancement going back to baseline values within 1 hour. The competition study showed a similar enhancement pattern to the aforementioned Gd-DOTA group. The control groups remained constant over the 2 hours of monitoring. In conclusion, P975 allows in vivo target-specific noninvasive MR imaging of activated platelets.