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Contrast Media & Molecular Imaging
Volume 2018, Article ID 6508724, 10 pages
https://doi.org/10.1155/2018/6508724
Research Article

111In-DANBIRT In Vivo Molecular Imaging of Inflammatory Cells in Atherosclerosis

1Radiopharmaceutical Sciences, University of New Mexico (UNM), Albuquerque, NM, USA
2Department of Surgery, Division of Vascular Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
3Pharmaceutical Sciences, UNM, Albuquerque, NM, USA
4Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
5Department of Biochemistry & Molecular Biology, School of Medicine, UNM, Albuquerque, NM, USA
6InviCRO, Boston, MA, USA
7Department of Anesthesiology and Critical Care Medicine, School of Medicine, UNM, Albuquerque, NM, USA

Correspondence should be addressed to Jeffrey P. Norenberg; ude.mnu.dulas@grebneronj

Received 29 June 2018; Revised 24 September 2018; Accepted 23 October 2018; Published 13 November 2018

Academic Editor: Anne Roivainen

Copyright © 2018 Roberto Mota et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Atherosclerosis-related morbidity and mortality remain a global concern. Atherosclerotic disease follows a slow and silent progression, and the transition from early-stage lesions to vulnerable plaques remains difficult to diagnose. Inflammation is a key component of the development of atherosclerotic plaque and consequent life-threatening complications. This study assessed 111In-DANBIRT as an in vivo, noninvasive SPECT/CT imaging probe targeting an inflammatory marker, Lymphocyte Function Associated Antigen-1 (LFA-1), in atherosclerotic plaques. Methods. Selective binding of 111In-DANBIRT was assessed using Sprague-Dawley rats exposed to filtered air and ozone (1 ppm) by inhalation for 4 hours to induce a circulating leukocytosis and neutrophilia in peripheral blood. After 24 hours, whole blood was collected and incubated with radiolabeled DANBIRT (68Ga-DANBIRT and 111In-DANBIRT). Isolated cell component smeared slides using cytospin technique were stained with Wright-Giemsa stain. Apolipoprotein E-deficient (apoE−/−) mice were fed either a normal diet or a high-fat diet (HFD) for 8 weeks. Longitudinal SPECT/CT imaging was performed 3 hours after administration at baseline, 4, and 8 weeks of HFD diet, followed by tissue harvesting for biodistribution, serum lipid analysis, and histology. 3D autoradiography was performed in both groups 24 hours after administration of 111In-DANBIRT. Results. Increased specific uptake of radiolabeled DANBIRT by neutrophils in the ozone-exposed group was evidenced by the acute immune response due to 4-hour ozone exposure. Molecular imaging performed at 3 hours using SPECT/CT imaging evidenced an exponential longitudinal increase in 111In-DANBIRT uptake in atherosclerosis lesions in HFD-fed mice compared to normal-diet-fed mice. Such results were consistent with increased immune response to vascular injury in cardiovascular and also immune tissues, correlated by 24 hours after administration of 3D autoradiography. Histologic analysis confirmed atherosclerotic disease progression with an increased vascular lesion area in HFD-fed mice compared to normal-diet-fed mice. Conclusion. 111In-DANBIRT is a promising molecular imaging probe to assess inflammation in evolving atheroma and atherosclerotic plaque.