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Potential of 99mTc-LDLs labeled by two different methods for scintigraphic detection of experimental atherosclerosis in rabbits

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Author: Atsma, D.E. · Feitsma, R.I.J. · Camps, J. · Hooft, F.M. van 't · Wall, E.E. van der · Nieuwenhuizen, W. · Pauwels, E.K.J.
Institution: Gaubius Laboratory Instituut voor verouderings- en vaatziekten onderzoek TNO
Source:Arteriosclerosis, Thrombosis and Vascular Biology, 1, 13, 78-83
Identifier: 232139
Keywords: Biology · LDL · Rradiolabeling · Scintigraphy · Dithionite · Low density lipoprotein · Sodium borohydride · Stannous chloride · Technetium 99m · Borane derivative · Borohydride potassium · Diagnostic agent · Technetium complex · Technetium Tc 99m low density lipoprotein · Technetium Tc 99m low-density lipoprotein · Abdominal aorta · Animal experiment · Animal model · Animal tissue · Clearance · Controlled study · Intermethod comparison · Isotope labeling · Scintiscanning · Thoracic aorta · Animal · Aorta · Arteriosclerosis · Borohydrides · Dithionite · Lipoproteins, LDL · Male · Organotechnetium Compounds · Rabbits · Support, Non-U.S. Gov't · Tin


In this study we evaluated two different 99mTc-labeling techniques to produce 99mTc-low density lipoprotein (99mTc-LDL) suitable for the scintigraphic delineation of experimental atherosclerotic lesions. The two methods are 1) a procedure that uses stannous chloride and sodium borohydride (borohydride method) and 2) a procedure that uses sodium dithionite as a reducing agent and that has been successfully applied in previous scintigraphic atherosclerosis detection (dithionite method). 99mTc-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 99mTc-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 99mTc over their entire length with either 99mTc-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 99mTc-LDL. For the dithionite method this 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 99mTc-LDL complexes, with 72% and 68% of the 99mTc 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 99mTc-LDL that accumulates in atherosclerotic lesions to the same extent 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. Chemicals/CAS: dithionite, 14844-07-6; sodium borohydride, 16940-66-2; stannous chloride, 7772-99-8; technetium 99m, 14133-76-7; tin, 14314-35-3, 7440-31-5; Borohydrides; Dithionite, 14844-07-6; Lipoproteins, LDL; Organotechnetium Compounds; potassium borohydride, 13762-51-1; stannous chloride, 7772-99-8; technetium Tc 99m low-density lipoprotein; Tin, 7440-31-5