Abstract 14063: Detection of Pulmonary Embolism with a Single-chain Antibody functionalized for Magnetic Resonance Imaging
Introduction: Pulmonary embolism is associated with high rates of morbidity and mortality. A major limitation of currently used diagnostic techniques, computed tomography or nuclear ventilation-perfusion imaging, is exposure to radiation. Radiation-free magnetic resonance imaging (MRI) still cannot provide the diagnostic sensitivity and accuracy needed especially within the lung tissue
Here, we use molecular imaging and MRI to specifically target and non-invasively depict sites of platelet activation in murine pulmonary thromboemboli using a functionalized single-chain antibody against ligand induced binding sites of activated platelets (LIBS).
Methods/Results: Injecting 5% thrombin solution intravenously induced reliable platelet-rich thromboemboli in pulmonary arteries as confirmed by ex vivo immunohistochemistry for CD41 (thrombin 5%: 4.3 ± 0.3 emboli per lobe vs. saline: 0.4 ± 0.2, p< 0.01). We then injected LIBS antibody functionalized with microparticles of iron oxide (LIBS-MPIO) after induction of pulmonary embolism. LIBS-MPIO specifically targeted pulmonary thromboemboli compared to injection of unspecific control-antibody (LIBS-MPIO: 9.8 ± 5.3 MPIO/ FOV vs. Control-MPIO: 0.45 ± 0.17, p< 0.01).
Performing in vivo molecular MRI, we detected local parenchymal edema after 5% thrombin solution most likely due to vessel obstruction.
In T2* weighted MRI scans of the lung before and after LIBS-MPIO injection we found locally restricted signal voids within the edematous area. Ex vivo we confirmed that LIBS-MPIO labeled thromboemboli correlated histologically with the area of the signal void.
Conclusions: We here demonstrate delivery and binding of LIBS-MPIO to activated platelets in pulmonary thromboembolism. Using molecular MRI we detected MPIO-induced signal voids that correlated with the presence of a vascular thrombus with in a local edema caused by this pathology.
Going forward, this molecular imaging approach may provide new opportunities to increase sensitivity of standard magnetic resonance imaging for detection of pulmonary embolism with implications for clinical translation.
Author Disclosures: T. Heidt: None. S. Ehrismann: None. K. Peter: None. C. Hagemeyer: None. I. Neudorfer: None. D. von Elverfeldt: None. C. Bode: None. C. von zur Muhlen: None.
- © 2014 by American Heart Association, Inc.