Imaging of atherosclerosis, targeting LFA-1 on inflammatory cells with 111 In-DANBIRT

J Nucl Cardiol. 2019 Oct;26(5):1697-1704. doi: 10.1007/s12350-018-1244-5. Epub 2018 Mar 13.

Abstract

Background: 111In-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 results: ApoE-/- 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.

Conclusions: Our results indicate the potential of radiolabeled DANBIRT as a relevant imaging radioligand for non-invasive evaluation of atherosclerotic inflammation.

Keywords: Atherosclerosis; SPECT; inflammation; molecular imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Azo Compounds / pharmacology
  • Female
  • Hydantoins / metabolism*
  • Immunohistochemistry
  • Indium Radioisotopes / metabolism*
  • Inflammation / diagnostic imaging
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Single Photon Emission Computed Tomography Computed Tomography

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Azo Compounds
  • CD68 protein, mouse
  • DOTA-1-(4-aminobutyl)-5-(4-bromobenzyl)-3-(3,5-dichlorophenyl)-5-methylimidazolidine-2,4-dione
  • Hydantoins
  • Indium Radioisotopes
  • Lymphocyte Function-Associated Antigen-1
  • Indium-111
  • oil red O