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Uptake of ¹¹¹In-Z2D3 on SPECT Imaging in a Swine Model of Coronary Stent Restenosis Correlated with Cell Proliferation

¹ Division of Cardiology, Department of Medicine, Rhode Island Hospital, Brown University, Providence, Rhode Island
² Armed Forces Institute of Pathology, Washington, D.C.
³ Northeastern University, Boston, Massachusetts

Small targets such as cell proliferation in the coronary arteries may potentially be detected with single-photon imaging using high-radiotracer-specific activity. We hypothesized that an antibody linked to polymers to increase specific radioactivity can be visualized on SPECT images and that counts in the target will correlate with the strength of the biologic signal. Methods: Twenty-four stents were placed using the balloon overexpansion technique in the coronary arteries of 14 juvenile domestic swine. One week later, the animals received 74 MBq of ¹¹¹In-diethylenetriaminepentaacetic acid-polylysine Z2D3-F(ab`)₂, and SPECT imaging was performed at 24 h. The coronary vessels were removed, and the stented vessels were processed with plastic embedding and sectioning. Medial and neointimal areas, percentage of vessel stenosis, and cell proliferation indices were quantified using a 5-bromo-2-deoxyuridine (BrdU) labeling index. Reconstructed SPECT images were interpreted for tracer uptake in coronary vessels. Results: Sixteen of the vessels were positive on SPECT imaging and 10 were negative. The percentage injected dose was 0.85 ± 0.28 x 10^-3 in scan-positive vessels and 0.34 ± 0.11 x 10^-3 in scan-negative vessels (P < 0.001). The medial-plus-neointimal proliferative index was 42 ± 11 in scan-positive vessels and 11 ± 11 in scan-negative vessels (P < 0.0001). The percentage stenoses were 21% ± 22% versus 19% ± 15% (not statistically significant). When individual values for the stented-to-control vessel counts were plotted against BrdU labeling index, a significant relationship was found (r² = 0.441; P = 0.0014). Conclusion: These data indicate that small targets relevant to human coronary vascular disease may be detected using polymer-modified radiolabeled antibodies.

Key Words: coronary artery • in-stent restenosis • smooth muscle cells • radiolabeled antibody fragments

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				B.-A. Khaw, Y. Tekabe, and L. L. Johnson Imaging Experimental Atherosclerotic Lesions in ApoE Knockout Mice: Enhanced Targeting with Z2D3-Anti-DTPA Bispecific Antibody and 99mTc-Labeled Negatively Charged Polymers J. Nucl. Med., May 1, 2006; 47(5): 868 - 876. [Abstract] [Full Text] [PDF]

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