Morris Timothy A, Marsh James J, Chiles Peter G, Konopka Ronald G, Pedersen Craig A, Schmidt Peter F, Gerometta Michael
Division of Pulmonary/Critical Care Medicine, Department of Medicine, University of California San Diego Medical Center, 200 West Arbor Drive, San Diego, CA 92103-8378, USA.
Am J Respir Crit Care Med. 2004 May 1;169(9):987-93. doi: 10.1164/rccm.200306-735OC. Epub 2004 Feb 12.
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.
以往尝试使用放射性标记抗体和核医学成像来诊断血栓栓塞的结果并不理想。我们展示了使用静脉注射的99m锝标记的去免疫抗纤维蛋白Fab'片段,通过单光子发射计算机断层扫描(SPECT,一种高度灵敏的闪烁成像技术)来诊断血栓栓塞的实验结果。在五只犬中形成肺栓塞(PEs)和下肢深静脉血栓(DVTs),然后经前肢静脉注射99m锝标记的Fab'(约400mg,约260MBq)。在注入抗体后每隔2小时进行胸部和下肢SPECT扫描,以显示血栓栓塞情况。注入抗体4小时后,所有质量为0.4g或更大的PEs和DVTs在SPECT扫描中分别清晰显示为肺内和腿部的“热点”。PEs(0.48±0.09g)被强烈放射性标记,凝块/血液放射性比值为22.8±5.6。DVTs(0.45±0.31g)也有较高的凝块/血液比值(11.7±2.6)。注入这些放射性标记的抗体片段并结合SPECT,可在临床可行的时间范围内清晰显示PEs和DVTs的图像。该技术甚至能可靠地识别相对较小的外周血栓栓塞,而这用目前可用的成像技术很难诊断,并且可能使同一患者的PEs、DVTs或两者都能成像。