Abstract 12153: Noninvasive Diagnosis of Ventricular Assist Device Thrombosis Using Fibrin-Specific Nuclear Imaging
Background: LVADs offer considerable benefit to patients with severe HF, but they are associated with complications: bleeding, infections, and thrombosis. GI bleeding and driveline infections are diagnosed and treated readily, but intrapump thrombosis is inferred only from nonspecific markers, such as serum LDH.
Objective: To develop a high avidity anti-fibrin nuclear probe designed to localize and quantify thrombus in high shear axial-flow pumps.
Materials: Monomeric bifunctional ligands with a fibrin-specific peptide, a short spacer, and technetium chelating amino acid sequence (F1A) were covalently intercoupled via a 4-arm-PEG2000-tetramer to form F4A. The F1A and F4A were radiolabeled with 99mTc using the IsoLink procedure.
Results: While 99mTc-F1A bound to fibrin with a Kd~4.5 nm, 99mTc-F4A bound more avidly and could not be displaced by F1A competition at a ratio of 120,000:1. In the presence of 50% serum, binding of 99mTc-F1A to fibrin clots was impaired (p≤0.05); no serum interference was detected for 99mTc-F4A (p>0.05). Pharmacokinetic studies over 180min in mice (n=3/treatment) revealed an improved beta-elimination half-life of 124±41min for 99mTc-F4A versus 176±26min for 99mTc-F1A. 99mTc-F1A and 99mTc-F4A were cleared into urine rapidly with negligible liver or spleen accumulation. In vivo studies in mice (n=3/treatment) with carotid thrombus induced by laser injury in the presence of Rose Bengal demonstrated thrombus signal with 99mTc-F4A at both 16μCi and 32μCi doses, which was competitively reduced by 30 to 50% with excess unlabeled F4A. LVAD titanium (1mm) housing attenuated the gamma rays by 20%, and this effect was similar in the inlet, turbine, and outlet LVAD compartments.
Conclusion: A novel, fibrin-specific 99mTc small tetrameric molecular imaging agent (99mTc-F4A) to detect, localize, and quantify LVAD thrombosis noninvasively was developed to provide direct diagnosis of LVAD thrombosis in this high-risk population.
- © 2013 by American Heart Association, Inc.