Abstract
Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism.
Highlights
Pulmonary thromboembolism (PE) is a mayor burden of morbidity and mortality worldwide, especially, if detected late or not at all[1,2]
In this study we investigate if targeting of activated platelets using microparticles of iron oxide (MPIO)-labeled single-chain antibodies can be used for the detection of murine pulmonary thromboembolism with magnetic resonance imaging
Based on vessel size and degree of vessel obstruction pulmonary thromboembolism were graded in four different size categories (Fig. 2a)
Summary
Pulmonary thromboembolism (PE) is a mayor burden of morbidity and mortality worldwide, especially, if detected late or not at all[1,2]. Standard techniques for detection of pulmonary embolism involve contrast-enhanced computed tomography or ventilation-perfusion szintigraphy[5,6]. Both techniques have proven high sensitivity and specificity for detection of pulmonary embolism, but involve radiation, which is unfavorable in young patients or if the pre-test probability is low. Molecular imaging with target specific imaging probes constitutes an emerging field because of its excellent possibilities to facilitate highly selective detection of epitopes even at very low density or in sparse contrast regions. Fibrin and alpha2-antiplasmin have previously been targeted in diverse formulations using gadolinium or perfluorocarbon compounds for contrast imaging and have shown promising results for the detection of venous thromboembolism[12,13,14]. With EP-2104R, fibrin-targeting has translated from bench to bedside, but a routine clinical application is still pending[15]
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