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

¹ Thomas Jefferson University, Philadelphia, Pennsylvania; and ² Palatin Technologies, Inc., Cranbury, New Jersey

Correspondence: For correspondence or reprints contact: Mathew L. Thakur, PhD, Radiology & Radiation Oncology, Radiopharmaceutical Research, Thomas Jefferson University, 1020 Locust St., Suite 359 JAH, Philadelphia, PA 19107. E-mail: mathew.thakur{at}jefferson.edu

A pentapeptide, Gly-Pro-Arg-Pro-Pro, with high affinity for -chain-fibrin was labeled with ^99mTc (^99mTc-TP850) and evaluated 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. DVT was 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 injection, heparinized, and sacrificed. Lungs were extirpated, radiographed, and imaged, and the PE was removed. Other tissues, 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 tissue. Results: The affinity for human fibrin was 10^–9 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 spontaneously below the spatial resolution of the -camera and, despite the high associated radioactivity, could not be localized in vivo. The fragmented clots were detectable by scintigraphy on excised lungs and provided excellent concordance with radiograms. Conclusion: ^99mTc-TP850 with its modest affinity (10^–9 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 peptide