In vivo technetium-99m S12 antibody imaging of platelet α-granules in rabbit endothelial neointimal proliferation after angioplasty

• Published in: Circulation (New York, N.Y.) Vol. 83; no. 1; pp. 224 - 236
• Main Authors: MILLER, D. D, BOULET, A. J, DADDONA, P. E, TIO, F. O, GARCIA, O. J, GUY, D. M, MCEVER, R. P, PALMAZ, J. C, KOON YAN PAK, NEBLOCK, D. S, BERGER, H. J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 1991
• Subjects: 550601 - Medicine- Unsealed Radionuclides in Diagnostics; ADHESION; Angioplasty, Balloon; ANIMAL TISSUES; ANIMALS; ANTIBODIES; Antibodies, Monoclonal; AORTA; ARTERIES; ARTERIOSCLEROSIS; Arteriosclerosis - diagnostic imaging; Arteriosclerosis - therapy; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; Blood and lymphatic vessels; BLOOD CELLS; BLOOD PLATELETS; Blood Platelets - metabolism; BLOOD VESSELS; BODY; BODY FLUIDS; Cardiology. Vascular system; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; Cell Adhesion Molecules - immunology; COUNTING TECHNIQUES; DIAGNOSIS; DIAGNOSTIC TECHNIQUES; DISEASES; Diseases of the aorta; ENDOTHELIUM; Endothelium, Vascular - injuries; GLYCOPROTEINS; HOURS LIVING RADIOISOTOPES; IN VIVO; INTERMEDIATE MASS NUCLEI; ISOMERIC NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; Male; MAMMALS; MATERIALS; Medical sciences; MONOCLONAL ANTIBODIES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; P-Selectin; Platelet Activation - physiology; Platelet Membrane Glycoproteins - immunology; PROTEINS; RABBITS; RADIOIMMUNODETECTION; RADIOIMMUNOSCINTIGRAPHY; RADIOISOTOPE SCANNING; RADIOISOTOPES; RADIOLOGY AND NUCLEAR MEDICINE; Radionuclide Imaging; SCINTISCANNING; SPECIFICITY; Stents; Technetium; TECHNETIUM 99; TECHNETIUM ISOTOPES; Thrombosis - diagnostic imaging; Thrombosis - etiology; TISSUES; TRACER TECHNIQUES; VASCULAR DISEASES; VERTEBRATES; YEARS LIVING RADIOISOTOPES; Radionuclide study; Rabbit; Instrumentation therapy; Cardiovascular disease; Exploration; Instrumental dilatation; Monoclonal antibody; Lagomorpha; Experimental study; Electron microscopy; Immunoradiodiagnosis; Endothelium; Abdominal aorta; Pathology; Vertebrata; Platelet; Mammalia; Animal; Atherosclerosis; Aortic disease
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.83.1.224

To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding. Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7). Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls). S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3). Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA. Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets. Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.