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

• Published in: American journal of respiratory and critical care medicine Vol. 169; no. 9; pp. 987 - 993
• Main Authors: Morris, Timothy A, Marsh, James J, Chiles, Peter G, Konopka, Ronald G, Pedersen, Craig A, Schmidt, Peter F, Gerometta, Michael
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.05.2004; American Lung Association; American Thoracic Society
• Subjects: Acute Disease; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies; Antibodies, Anti-Idiotypic; Anticoagulants; Balloon Occlusion - methods; Balloon Occlusion - standards; Biological and medical sciences; Chromatography; Disease Models, Animal; Dogs; Drug dosages; Drug Evaluation, Preclinical; Feasibility Studies; Immunoglobulin Fab Fragments - immunology; Intensive care medicine; Laboratory animals; Lungs; Male; Medical sciences; Nuclear medicine; Pulmonary Embolism - diagnostic imaging; Radioimmunodetection - methods; Radioimmunodetection - standards; Sensitivity and Specificity; Technetium - pharmacokinetics; Thromboembolism; Time Factors; Tissue Distribution; Tomography; Tomography, Emission-Computed, Single-Photon - methods; Tomography, Emission-Computed, Single-Photon - standards; Veins & arteries; Venous Thrombosis - diagnostic imaging; St Louis Missouri; United States > US; Intensive care; Computerized axial tomography; D dimer; Photon; Resuscitation; Emission tomography
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200306-735OC

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' ( approximately 400 mg, approximately 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.