In this study we evaluated two different""To-labeling techniques to produce "To-low density lipoprotein (99mTc-LDL) suitable for the scintigraphic delineation of experimental atherosclerotic lesions. The two methods are 1) a procedure that uses stamnous chloride and sodium borohydride (borohydride method) and 2) a procedure that uses sodium dithiionite as a reducing agent and that has been successfully applied in previous scintigraphic atherosclerosis; detection (dithionite method). ""Tc-LDL produced by either method was injected into New Zealand White rabbits with diet-induced atherosclerotic plaques and in control rabbits. Scintigraphic images were taken 10 minutes (t=0) and 1, 4, 8, 16, and 24 hours after injection. Clearance of plasma radioactivity was also studied. Stability of the " m Tc-LDL complex in the circulation was examined by size exclusion chromatography of plasma samples. After scintigraphy, the animals were killed, and the biodistribution of radioactivity was determined. The thoracic and abdominal aortas appeared in scintigraphic images to accumulate " m Tc over their entire length with either "Tc-LDL preparation. The sparse imaging of focal atherosclerosis was found to be due to the fact that the aortas were covered with confluent atherosclerotic lesions. Scintigraphic image analysis showed that 24 hours after injection, the accumulated radioactivity in the abdominal aorta of the atherosclerotic rabbits was 57% and 54%, respectively, of the accumulated radioactivity in the abdominal aorta at t=0 when the borohydride versus the dithionite method was used. In the control animals this value was 25% for the dithionite method, whereas in the borohydride method the aortas could not be detected in the images at t=24 hours. When the borohydride method was used, radioactivity in the abdominal aorta in the atherosclerotic animals was significantly higher than in control rabbits 4 hours after injection of the "Tc-LDL. For the dithionite method (his was 16 hours after injection. Plasma radioactivities in atherosclerotic animals at t=24 hours were 28% and 41% of plasma radioactivity at t=0 for the borohydride and the dithionite method, respectively. In control animals these values were 6% and 18%, respectively. Both methods produced relatively stable "Tc-LDL complexes, with 72% and 68% of the """Tc remaining attached to LDL at t=24 hours. In the biodistribution study, uptake of radioactivity in the aortas was comparable for both labeling methods. We conclude that the borohydride method may be useful in the scintigraphic detection of atherosclerosis, since it yields "Tc-LDL that accumulates in atherosclerotic lesions to the same extend as LDL labeled by the dithionite method. In addition, it is cleared from the circulation considerably faster, resulting more rapidly in a higher target-to-nontarget ratio, which facilitates early identification of atherosclerosis.