Author/Authors :
Mota, Roberto Department of Surgery - Division of Vascular Surgery - University of North Carolina at Chapel Hill - Chapel Hill, USA , Campen, Matthew J Pharmaceutical Sciences - Albuquerque, USA , Cuellar, Matthew E University of Minnesota - Minneapolis, USA , Garver, William S Department of Biochemistry & Molecular Biology - School of Medicine - Albuquerque, USA , Hesterman, Jacob InviCRO - Boston, USA , Qutaish, Mohammed InviCRO - Boston, USA , Daniels, Tamara University of New Mexico (UNM) - Albuquerque, USA , Nysus, Monique University of New Mexico (UNM) - Albuquerque, USA , Wagner, Carston R University of Minnesota - Minneapolis, USA , Norenberg, Jeffrey P University of New Mexico (UNM) - Albuquerque, USA
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 dificult to diagnose. Inflammation is a key
component of the development of atherosclerotic plaque and consequent life-threatening complications. is 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 ltered 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 (68GaDANBIRT and 111In-DANBIRT). Isolated cell component smeared slides using cytospin technique were stained with WrightGiemsa stain. Apolipoprotein E-decient (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 specic 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 conrmed 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.
Keywords :
111In-DANBIRT , Cell , Vivo , HPLC
