Scintigraphic detection of acute experimental endocarditis with the technetium-99m labelled glycoprotein IIb/IIIa receptor antagonist DM P444

Bacterial endocarditis is an important clinical problem that may result in persistent bacteraemia and irreversible cardiac damage. Since endocarditis is char acterized by aggregation of activated platelets, fibrin and bacteri a, we studied DMP444, a technetium-99m labelled high-affinity antagonist of the GP IIb/IIIa receptor that is expressed on activated platelets. In seve n Beagle dogs (11-15 kg), the left ventricle was catheterized via the right carotid artery. One hour later. 5 x 10(7) colony forming units of Staphylo coccus aureus were injected intracardially. Half an hour later, the cathete r was removed. Two extra dogs underwent a complete sham procedure. One day after the intervention, five infected and the two non-infected dogs were in jected with 37 MBq/kg Tc-99m-DMP444 and two infected dogs with 37 MBq/kg Tc -99m-IgG (used as a non-specific control agent) and imaged up to 4 h after injection. Samples were obtained for tissue counting, microbiology and hist ology. From 1 to 2 h post injection onward, there was clear focal accumulat ion of DMP444 in the aortic valve region when endocarditis was present, and this accumulation increased with time. The non-infected and the Tc-99m-IgG injected dogs showed only persisting blood pool activity without any focal abnormality. At 4 h post injection, the in vivo valve-to-blood pool ratios were 1.87 +/- 0.18 in endocarditis, 1.01 +/- 0.05 in non-infected controls and 1.09 +/- 0.02 in Tc-99m-IgG injected dogs (P < 0.05). It is concluded that targeting activated platelets with the Tc-99m-labelled GP IIb/IIIa ant agonist DMP444 allows a final diagnosis of experimental bacterial endocardi tis within 4 h owing to high, specific and fast in vivo uptake.