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

Roberto Mota, Matthew J. Campen, Matthew E Cuellar, William S. Garver, Jacob Hesterman, Mohammed Qutaish, Tamara Daniels, Monique Nysus, Carston R Wagner, Jeffrey P. Norenberg

Research output: Contribution to journalArticle

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 111 In-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 111 In-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 ( 68 Ga-DANBIRT and 111 In-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 111 In-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 111 In-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. 111 In-DANBIRT is a promising molecular imaging probe to assess inflammation in evolving atheroma and atherosclerotic plaque.

Original languageEnglish (US)
Article number6508724
JournalContrast Media and Molecular Imaging
Volume2018
DOIs
StatePublished - Jan 1 2018

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Molecular Imaging
High Fat Diet
Atherosclerotic Plaques
Atherosclerosis
Ozone
Diet
Apolipoproteins E
Autoradiography
Tissue and Organ Harvesting
Azure Stains
Inflammation
Molecular Probes
Lymphocyte Function-Associated Antigen-1
Vascular System Injuries
Leukocytosis
Cellular Structures
Inhalation
Blood Vessels
Sprague Dawley Rats
Disease Progression

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Mota, R., Campen, M. J., Cuellar, M. E., Garver, W. S., Hesterman, J., Qutaish, M., ... Norenberg, J. P. (2018). 111 In-DANBIRT in Vivo Molecular Imaging of Inflammatory Cells in Atherosclerosis Contrast Media and Molecular Imaging, 2018, [6508724]. https://doi.org/10.1155/2018/6508724

111 In-DANBIRT in Vivo Molecular Imaging of Inflammatory Cells in Atherosclerosis . / Mota, Roberto; Campen, Matthew J.; Cuellar, Matthew E; Garver, William S.; Hesterman, Jacob; Qutaish, Mohammed; Daniels, Tamara; Nysus, Monique; Wagner, Carston R; Norenberg, Jeffrey P.

In: Contrast Media and Molecular Imaging, Vol. 2018, 6508724, 01.01.2018.

Research output: Contribution to journalArticle

Mota, R, Campen, MJ, Cuellar, ME, Garver, WS, Hesterman, J, Qutaish, M, Daniels, T, Nysus, M, Wagner, CR & Norenberg, JP 2018, '111 In-DANBIRT in Vivo Molecular Imaging of Inflammatory Cells in Atherosclerosis ' Contrast Media and Molecular Imaging, vol. 2018, 6508724. https://doi.org/10.1155/2018/6508724
Mota, Roberto ; Campen, Matthew J. ; Cuellar, Matthew E ; Garver, William S. ; Hesterman, Jacob ; Qutaish, Mohammed ; Daniels, Tamara ; Nysus, Monique ; Wagner, Carston R ; Norenberg, Jeffrey P. / 111 In-DANBIRT in Vivo Molecular Imaging of Inflammatory Cells in Atherosclerosis In: Contrast Media and Molecular Imaging. 2018 ; Vol. 2018.
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title = "111 In-DANBIRT in Vivo Molecular Imaging of Inflammatory Cells in Atherosclerosis",
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 111 In-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 111 In-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 ( 68 Ga-DANBIRT and 111 In-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 111 In-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 111 In-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. 111 In-DANBIRT is a promising molecular imaging probe to assess inflammation in evolving atheroma and atherosclerotic plaque.",
author = "Roberto Mota and Campen, {Matthew J.} and Cuellar, {Matthew E} and Garver, {William S.} and Jacob Hesterman and Mohammed Qutaish and Tamara Daniels and Monique Nysus and Wagner, {Carston R} and Norenberg, {Jeffrey P.}",
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AU - Mota, Roberto

AU - Campen, Matthew J.

AU - Cuellar, Matthew E

AU - Garver, William S.

AU - Hesterman, Jacob

AU - Qutaish, Mohammed

AU - Daniels, Tamara

AU - Nysus, Monique

AU - Wagner, Carston R

AU - Norenberg, Jeffrey P.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 111 In-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 111 In-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 ( 68 Ga-DANBIRT and 111 In-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 111 In-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 111 In-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. 111 In-DANBIRT is a promising molecular imaging probe to assess inflammation in evolving atheroma and atherosclerotic plaque.

AB - 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 111 In-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 111 In-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 ( 68 Ga-DANBIRT and 111 In-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 111 In-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 111 In-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. 111 In-DANBIRT is a promising molecular imaging probe to assess inflammation in evolving atheroma and atherosclerotic plaque.

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