Published ahead of print on February 12, 2004, doi:10.1164/rccm.200306-735OC Am. J. Respir. Crit. Care Med., Volume 169, Number 9, May 2004, 987-993 A more recent version of this article appeared on May 1, 2004
Submitted on June 9, 2003 Single Photon Emission Computed Tomography of Pulmonary Emboli and Venous Thrombi Using Anti-D-dimerTimothy A Morris1*,1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, CA, USA, 2 Agen Biomedical Ltd., Acacia Ridge, Queensland, Australia * To whom correspondence should be addressed. 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 99mTc labeled deimmunized anti-fibrin Fab[[rad]] 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 99mTc-labeled Fab[[rad]] (~400 mg, ~260 MBq) were injected via forelimb veins. Thoracic and lower extremity SPECT scans were performed at two-hour intervals after antibody infusion in order to visualize the thromboemboli. Four hours after antibody infusion, all PEs and DVTs of mass 0.4 grams or greater were clearly visualized on SPECT scans as "hot spots" within the lungs and legs, respectively. PEs (0.48 ± 0.09 grams) were intensely radiolabeled, yielding clot/blood radioactivity ratios of 22.8 ± 5.6. DVTs (0.45 ± 0.31 grams) 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. Key words: pulmonary embolism, diagnosis, thromboembolism.
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