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J Nucl Cardiol. 2018 Mar 13. doi: 10.1007/s12350-018-1244-5. [Epub ahead of print]

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

Author information

1
Department of Biomedical Engineering, Thorax Center, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
2
Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
3
Department of Cardiology, Thorax Center, Erasmus Medical Center, Rotterdam, The Netherlands.
4
Radiopharmaceutical Sciences, University of New Mexico, Albuquerque, NM, USA.
5
Department of Biomedical Engineering, Thorax Center, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. k.vanderheiden@erasmusmc.nl.

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

PMID:
29536351
DOI:
10.1007/s12350-018-1244-5

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