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

D. D. Miller, A. J. Boulet, F. O. Tio, O. J. Garcia, D. M. Guy, R. P. McEver, J. C. Palmaz, K. Y. Pak, D. S. Neblock, H. J. Berger, P. E. Daddona

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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 < 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 < 0.05 versus controls). S12 antibody uptake decreased significantly (p < 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 α-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.

Original languageEnglish (US)
Pages (from-to)224-236
Number of pages13
JournalCirculation
Volume83
Issue number1
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

Keywords

  • atherosclerosis
  • monoclonal antibodies
  • percutaneous transluminal angioplasty
  • platelets
  • radionuclide imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Miller, D. D., Boulet, A. J., Tio, F. O., Garcia, O. J., Guy, D. M., McEver, R. P., Palmaz, J. C., Pak, K. Y., Neblock, D. S., Berger, H. J., & Daddona, P. E. (1991). In vivo technetium-99m S12 antibody imaging of platelet α-granules in rabbit endothelial neointimal proliferation after angioplasty. Circulation, 83(1), 224-236. https://doi.org/10.1161/01.CIR.83.1.224