Technetium-99m-labeled recombinant tissue plasminogen activator for the imaging of emboli in vivo

Tissue-type plasminogen activator (t-PA) effectively lyses active thrombus by direct action. Recombinant t-PA (rt-PA) was labeled with technetium-99m (99mTc) to investigate the in vivo binding to fibrin clots in a feline cerebral embolism model created by insertion of an artificial fibrin clot within the carotid artery. 99mTc-rt-PA administered intravenously provided clearer imaging of clots after priming with cold rt-PA, with uptake peaking 5-10 minutes after the injection. 99mTc-labeled human serum albumin was not retained at clot sites. Systemically administered 99mTc-rt-PA binds to fibrin clots within carotid arteries in our feline model. Our results suggest that the interaction of intrinsic plasminogen activator inhibitors with extrinsically administered rt-PA may regulate the demonstration of a clot, although the precise mechanism is unclear.