Pretargeting of bacterial endocarditis in rats with streptavidin and 111In-labeled biotin

A radioimaging approach for the detection of endocarditis has been investigated using two-step pretargeting with streptavidin and radiolabeled biotin.

Hemodynamic alterations within the rat heart were induced by placing an in-dwelling catheter into the left ventricle through the aortic valves. The animals were subsequently infected with Staphylococcus aureus through a tail vein. After an incubation period, rats were first injected with streptavidin and, 2 h later, with 111In-labeled ethylene-diaminetetraacetic acid-biotin. Whole-body gamma camera images were taken 4-5 h postinjection of the radiolabeled biotin. Control animals consisted of catheterized but uninfected, infected but uncatheterized and normal untreated rats. As a further control, the labeled biotin was administered to a study animal without the preadministration of streptavidin.

Histology showed typical endocarditic changes in the hearts of study animals with massive deposition of gram-positive cocci. Catheterized but uninfected animals showed alterations corresponding to nonbacterial thrombotic endocarditis. Macroautoradiography showed accumulation of radiolabel in the endocarditic vegetations of study animals. Whole-body gamma camera images showed important cardiac uptake in 7 of 8 catheterized and infected animals and in 3 of 6 catheterized but uninfected animals. Normal rats and those infected but not catheterized showed negative results by histology, autoradiography and imaging. The percent uptake of the injected dose in the heart was 0.20 (SD = 0.13) in catheterized and infected animals, 0.12 (SD = 0.10) in catheterized but uninfected animals, 0.10 (SD = 0.04) in infected but uncatheterized animals and 0.04 (SD = 0.01) in normal control animals.

The two-step pretargeting approach using streptavidin and 111In-labeled biotin was used successfully to detect S. aureus-induced bacterial endocarditis in rats.