Studies of ^99mTc-acylplasmins as agents for thrombus detection

It has been proposed that acylation at the active site of plasmin is able to prevent its reaction with α2-antiplasmin without affecting the fibrin affinity of the enzyme. To investigate the possibility that ^99mTc-labelled acylplasmins are improved thrombus-detecting agents, six acylating agents were synthesised and their reaction with plasmin and the labelling of the products with ^99mTc studies. Uptake of ^99mTc-acylplasmins in an in vitro thrombus model was complicated by precipitation processes, which may in part account for the rapid blood clearance in rabbits and high liver uptake in mice injected with the compounds. Quantitative measurements using an in vivo rabbit thrombus model demonstrated that guanidinobenzoyl-plasmin exhibited nearly a threefold increase in thrombus uptake compared with non-acylated ^99mTc-plasmin. The observed uptake is less than that obtained with ¹²⁵I-fibrinogen at clinically useful time intervals post-injection but represents a significant advantage over the use of ^99mTc-plasmin.