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Published ahead of print on February 12, 2004, doi:10.1164/rccm.200306-735OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 987-993, (2004)
© 2004 American Thoracic Society

Single Photon Emission Computed Tomography of Pulmonary Emboli and Venous Thrombi Using Anti–D-Dimer

Timothy A. Morris, James J. Marsh, Peter G. Chiles, Ronald G. Konopka, Craig A. Pedersen, Peter F. Schmidt and Michael Gerometta

Division of Pulmonary/Critical Care Medicine, Department of Medicine, University of California San Diego, San Diego, California; and Agen Biomedical Ltd, Queensland, Australia

Correspondence and requests for reprints should be addressed to Timothy A. Morris, M.D., Associate Professor of Medicine, University of California San Diego Medical Center, 200 West Arbor Drive, San Diego, CA 92103-8378. E-mail: t1morris{at}ucsd.edu

Previous attempts to diagnose thromboemboli using radiolabeled antibodies and nuclear medicine imaging have been disappointing. We present the results of experiments with intravenous technetium-99m–labeled deimmunized antifibrin Fab' fragments to diagnose thromboemboli using single photon emission computed tomography (SPECT), a highly sensitive scintigraphic imaging technique. Pulmonary emboli (PEs) and lower extremity deep vein thrombi (DVTs) were formed in five dogs, then technetium-99m–labeled Fab' (~ 400 mg, ~ 260 MBq) were injected via forelimb veins. Thoracic and lower extremity SPECT scans were performed at 2-hour intervals after antibody infusion to visualize the thromboemboli. Four hours after antibody infusion, all PEs and DVTs of mass 0.4 g or greater were clearly visualized on SPECT scans as ‘hot spots’ within the lungs and legs, respectively. PEs (0.48 ± 0.09 g) were intensely radiolabeled, yielding clot/blood radioactivity ratios of 22.8 ± 5.6. DVTs (0.45 ± 0.31 g) also had high clot/blood ratios (11.7 ± 2.6). Infusion of these radiolabeled antibody fragments, combined with SPECT, produces clear images of PEs and DVTs within a clinically feasible time frame. The technique reliably identified even peripheral thromboemboli of relatively small size, which are difficult to diagnose with currently available imaging techniques, and may enable imaging of PEs, DVTs, or both in the same patient.




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