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In Vivo Uptake of Radiolabeled Antibody to Proliferating Smooth Muscle Cells in a Swine Model of Coronary Stent Restenosis

Division of Cardiology, Department of Medicine, Rhode Island Hospital, Providence, Rhode Island
Armed Forces Institute of Pathology, Washington, DC
Northeastern University, Boston, Massachusetts

Correspondence: For correspondence or reprints contact: Lynne L. Johnson, MD, Rhode Island Hospital Main Bldg., Rm. 208,593 Eddy St., Providence, RI 02903.

ABSTRACT

Z2D3 is a monoclonal chimeric antibody fragment that is directed against a protein expressed on the surface of proliferating smooth muscle cells. The purpose of this study was to investigate the uptake of ¹¹¹In-labeled Z2D3 F(ab')₂ in a swine model of coronary neointimal proliferation after overexpansion coronary stenting. Methods: Twenty-two domestic swine underwent over-expansion coronary stenting of 2 vessels. Fifteen swine survived 2–4 wk, at which time they received an injection of ¹¹¹In Z2D3 F(ab')₂ and underwent planar imaging. After the swine were killed, the hearts were excised and imaged on the detector. The cross-sectional area of each stented vessel was measured with digital morphometry. Results: Pathology could be correlated with imaging for 24 vessels. The cross-sectional area of stenosis comprising neointimal proliferation ranged from 8% to 95%, with a mean ± SD of 41% ± 21%. The maximal stenosis ranged from 13% to 95%, with a mean of 51% ± 20%. Seventeen of 24 vessels (71%) showed focal uptake on in vivo imaging, and 7 of 24 (29%) did not. Twenty of 24 (83%) showed uptake on ex vivo imaging. Of 11 stented vessels with maximal vessel stenosis less than 50%, 7 (64%) showed uptake both in vivo and ex vivo, and of 13 stented vessels with maximal vessel stenosis greater than 50%, 10 (77%) showed uptake both in vivo and ex vivo. Conclusion: Uptake of a radiolabeled antibody directed against a component of proliferating neointimal tissue can be visualized in the coronary arteries on in vivo imaging using a scintillation gamma camera.

Key Words: coronary stents • restenosis • swine • monoclonal antibodies

This article has been cited by other articles:

				J. Jimenez, T. Donahay, L. Schofield, B. A. Khaw, and L. L. Johnson Smooth Muscle Cell Proliferation Index Correlates with 111In-Labeled Antibody Z2D3 Uptake in a Transplant Vasculopathy Swine Model J. Nucl. Med., March 1, 2005; 46(3): 514 - 519. [Abstract] [Full Text] [PDF]

				L. L. Johnson, L. M. Schofield, D. K. Weber, F. Kolodgie, R. Virmani, and B. A. Khaw Uptake of 111In-Z2D3 on SPECT Imaging in a Swine Model of Coronary Stent Restenosis Correlated with Cell Proliferation J. Nucl. Med., February 1, 2004; 45(2): 294 - 299. [Abstract] [Full Text] [PDF]