Tohoku J. Exp. Med., 2011, 223(1)

Detection of Pulmonary Embolism with 99mTc-Labeled F(ab)2 Fragment of Anti-P-Selectin Monoclonal Antibody in Dogs

SHUNDONG JI1, WEI FANG2, MINGQING ZHU1, XIA BAI1, CHEN WANG3 and CHANGGENG RUAN1

1Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, P.R. China
2Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China
3Beijing Chao Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, P.R. China

Pulmonary embolism is a common and potentially life-threatening condition, and its correct diagnosis is highly desirable before anticoagulant therapy is initiated. However, the safe and accurate diagnosis of acute pulmonary embolism remains a challenge. Single photon emission computed tomography (SPECT) is a highly sensitive scintigraphic imaging technique. Pulmonary embolism can be detected by SPECT with 99mTc-labeled imaging agents that bind to components present predominantly on thromboemboli. P-selectin is an adhesion glycoprotein that is expressed in platelets and endothelial cells. P-selectin on activated platelets is a suitable biomarker of the active thrombus process. The objective of this study was to evaluate 99mTc-labeled F(ab)2 fragment of anti-P-selectin monoclonal antibody SZ51, 99mTc-SZ51-F(ab)2, for imaging pulmonary embolism in beagle canines. SZ51 was digested to F(ab)2 fragment, named SZ51-F(ab)2, and its specific binding to P-selectin on either human or canine platelets was verified by flow cytometry assay. In each dog, an 18-gauge catheter was inserted into left or right pulmonary artery, and a two-stranded spiral stainless-steel coil (20 mm) was inserted through catheter. At 30 min after coil placement, X-ray angiography was performed to document the pulmonary embolism and the locations of the coil. After intravenous injection of 99mTc-SZ51-F(ab)2, experimental thrombi in dogs could be consistently visualized for 2-3 hours by SPECT. Pulmonary embolism showed higher uptake of 99mTc-SZ51-F(ab)2. The present study suggests that 99mTc-SZ51-F(ab)2 may be a promising agent for detecting pulmonary embolism.

keywords —— monoclonal antibody; pulmonary embolism; platelet; P-selectin; molecular imaging

===============================

Tohoku J. Exp. Med., 2011, 223, 9-15

Correspondence: Changgeng Ruan, M.D., Ph.D., Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, 215006, P.R. China.

e-mail: changgengruan@hotmail.com