Autoradiographical assessment of inflammation-targeting radioligands for atherosclerosis imaging: potential for plaque phenotype identification

Eric J Meester; Erik de Blois; Boudewijn J Krenning; Antonius F W van der Steen; Jeff P Norenberg; Kim van Gaalen; Monique R Bernsen; Marion de Jong; Kim van der Heiden

doi:10.1186/s13550-021-00772-z

Autoradiographical assessment of inflammation-targeting radioligands for atherosclerosis imaging: potential for plaque phenotype identification

EJNMMI Res. 2021 Mar 17;11(1):27. doi: 10.1186/s13550-021-00772-z.

Authors

Eric J Meester^{1

2}, Erik de Blois², Boudewijn J Krenning³, Antonius F W van der Steen¹, Jeff P Norenberg⁴, Kim van Gaalen¹, Monique R Bernsen², Marion de Jong², Kim van der Heiden⁵

Affiliations

¹ Department of Biomedical Engineering, Thorax Center, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
² Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
³ Department of Cardiology, Thorax Center, Erasmus MC, 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

Purpose: Many radioligands have been developed for the visualization of atherosclerosis by targeting inflammation. However, interpretation of in vivo signals is often limited to plaque identification. We evaluated binding of some promising radioligands in an in vitro approach in atherosclerotic plaques with different phenotypes.

Methods: Tissue sections of carotid endarterectomy tissue were characterized as early plaque, fibro-calcific plaque, or phenotypically vulnerable plaque. In vitro binding assays for the radioligands [¹¹¹In]In-DOTATATE; [¹¹¹In]In-DOTA-JR11; [⁶⁷Ga]Ga-Pentixafor; [¹¹¹In]In-DANBIRT; and [¹¹¹In]In-EC0800 were conducted, the expression of the radioligand targets was assessed via immunohistochemistry. Radioligand binding and expression of radioligand targets was investigated and compared.

Results: In sections characterized as vulnerable plaque, binding was highest for [¹¹¹In]In-EC0800; followed by [¹¹¹In]In-DANBIRT; [⁶⁷Ga]Ga-Pentixafor; [¹¹¹In]In-DOTA-JR11; and [¹¹¹In]In-DOTATATE (0.064 ± 0.036; 0.052 ± 0.029; 0.011 ± 0.003; 0.0066 ± 0.0021; 0.00064 ± 0.00014 %Added activity/mm², respectively). Binding of [¹¹¹In]In-DANBIRT and [¹¹¹In]In-EC0800 was highest across plaque phenotypes, binding of [¹¹¹In]In-DOTA-JR11 and [⁶⁷Ga]Ga-Pentixafor differed most between plaque phenotypes. Binding of [¹¹¹In]In-DOTATATE was the lowest across plaque phenotypes. The areas positive for cells expressing the radioligand's target differed between plaque phenotypes for all targets, with lowest percentage area of expression in early plaque sections and highest in phenotypically vulnerable plaque sections.

Conclusions: Radioligands targeting inflammatory cell markers showed different levels of binding in atherosclerotic plaques and among plaque phenotypes. Different radioligands might be used for plaque detection and discerning early from vulnerable plaque. [¹¹¹In]In-EC0800 and [¹¹¹In]In-DANBIRT appear most suitable for plaque detection, while [⁶⁷Ga]Ga-Pentixafor and [¹¹¹In]In-DOTA-JR11 might be best suited for differentiation between plaque phenotypes.

Keywords: Atherosclerosis; Autoradiography; Inflammation; Molecular imaging.

Grants and funding

MRace/Erasmus Medisch Centrum