Imaging Thromboembolism with Fibrin-Avid 99mTc-Peptide: Evaluation in Swine

A pentapeptide, Gly-Pro-Arg-Pro-Pro, with high affinity for a-chain-fibrin was labeled with 99mTc (99mTc-TP850) and evalu-ated in swine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE). Methods: Scatchard analysis was performed to determine fibrin affinity for TP850 and the number of binding sites (receptors) per milligram of fibrin. DVTwas induced in the left jugular vein and PE was induced by introducing a preformed autologous blood clot into the right atrium using a 7-French introducer sheath inserted into the right jugular vein. 99mTc-TP850 was injected at 4, 24, 48, 72, 96, or 120 h later. Animals were imaged for up to 4 h after in-jection, heparinized, and sacrificed. Lungs were extirpated, radiographed, and imaged, and the PE was removed. Other tis-sues, including blood and normal lungs, were harvested and, concomitantly, 99mTc was counted for determination of target-to-tissue ratios and the percentage injected dose per gram of tis-sue. Results: The affinity for human fibrin was 1029 mol/L and there were.1015 receptors per milligram of fibrin. DVT and PE were visualized for up to 4 h after injection with high DVT/blood (7.9–22.6), DVT/muscle (31.1–89.4), PE/blood (1–155), and PE/ lung (0.8–245) ratios. Thereafter, the PEs fragmented spontane-ously below the spatial resolution of the g-camera and, despite the high associated radioactivity, could not be localized in vivo. The fragmented clots were detectable by scintigraphy on ex-cised lungs and provided excellent concordance with radio-grams. Conclusion: 99mTc-TP850 with its modest affinity (1029 mol/L), rapid blood clearance, and high DVT and PE uptake is a promising agent for imaging vascular thrombosis. Key Words: imaging vascular thrombosis; imaging pulmonary embolism; imaging venous thrombosis; 99mTc-antifibrin peptid