Abstract
Background111In-DOTA-butylamino-NorBIRT (DANBIRT) is a novel radioligand which binds to Leukocyte Function-associated Antigen-1 (LFA-1), expressed on inflammatory cells. This study evaluated 111In-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice. Methods and ResultsApoE−/− mice, fed an atherogenic diet up to 20 weeks (n = 10), were imaged by SPECT/CT 3 hours post injection of 111In-DANBIRT (~ 200 pmol, ~ 40 MBq). Focal spots of 111In-DANBIRT were visible in the aortic arch of all animals, with an average Target-to-Background Ratio (TBR) of 1.7 ± 0.5. In vivo imaging results were validated by ex vivo SPECT/CT imaging, with a TBR up to 11.5 (range 2.6 to 11.5). Plaques, identified by Oil Red O lipid-staining on excised arteries, co-localized with 111In-DANBIRT uptake as determined by ex vivo autoradiography. Subsequent histological processing and in vitro autoradiography confirmed 111In-DANBIRT uptake at plaque areas containing CD68 expressing macrophages and LFA-1 expressing inflammatory cells. Ex vivo incubation of a human carotid endarterectomy specimen with 111In-DANBIRT (~ 950 nmol, ~ 190 MBq) for 2 hours showed heterogeneous plaque uptake on SPECT/CT, after which immunohistochemical analysis demonstrated co-localization of 111In-DANBIRT uptake and CD68 and LFA-1 expressing cells. ConclusionsOur results indicate the potential of radiolabeled DANBIRT as a relevant imaging radioligand for non-invasive evaluation of atherosclerotic inflammation.
Highlights
Cardiovascular disease remains the major cause of death worldwide.[1]
Focal spots of 111In-DANBIRT were visible in the aortic arch of all animals, with an average Target-to-Background Ratio (TBR) of 1.7 ± 0.5
In vivo imaging results were validated by ex vivo Single Photon Emission Computed Tomography (SPECT)/Computed Tomography (CT) imaging, with a TBR up to 11.5
Summary
Cardiovascular disease remains the major cause of death worldwide.[1]. Most cardiovascular events are a consequence of atherosclerosis, in which plaques form due to chronic inflammation and lipid accumulation in the vessel wall. Before rupture, would allow targeted treatment and prevention of a potentially life-threatening cardiovascular event. Inflammation is a major hallmark of atherosclerosis and a consistent predictor of cardiovascular risk.[2,3] The recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial showed that reduction of inflammation in patients after myocardial infarction could reduce the risk of new adverse cardiovascular events in the future.[4] Assessment of the severity of inflammation in atherosclerosis using biomarkers is cumbersome . High-sensitive C-reactive protein (hsCRP) is a prototypic marker of inflammation and a strong independent predictor for future cardiovascular events, yet is influenced by risk factors such as hypertension, smoking, and periodontal disease.[5] Noninvasive visualization of arterial inflammation may complement biomarkers such as hsCRP in guiding treatment with new anti-inflammatory drugs. This study evaluated 111In-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice
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