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Imaging inflammation in atherosclerotic plaques, targeting SST2 with [111In]In-DOTA-JR11.


ABSTRACT:

Background

Imaging Somatostatin Subtype Receptor 2 (SST2) expressing macrophages by [DOTA,Tyr3]-octreotate (DOTATATE) has proven successful for plaque detection. DOTA-JR11 is a SST2 targeting ligand with a five times higher tumor uptake than DOTATATE, and holds promise to improve plaque imaging. The aim of this study was to evaluate the potential of DOTA-JR11 for plaque detection.

Methods and results

Atherosclerotic ApoE-/- mice (n = 22) fed an atherogenic diet were imaged by SPECT/CT two hours post injection of [111In]In-DOTA-JR11 (~ 200 pmol, ~ 50 MBq). In vivo plaque uptake of [111In]In-DOTA-JR11 was visible in all mice, with a target-to-background-ratio (TBR) of 2.23 ± 0.35. Post-mortem scans after thymectomy and ex vivo scans of the arteries after excision of the arteries confirmed plaque uptake of the radioligand with TBRs of 2.46 ± 0.52 and 3.43 ± 1.45 respectively. Oil red O lipid-staining and ex vivo autoradiography of excised arteries showed [111In]In-DOTA-JR11 uptake at plaque locations. Histological processing showed CD68 (macrophages) and SST2 expressing cells in plaques. SPECT/CT, in vitro autoradiography and immunohistochemistry performed on slices of a human carotid endarterectomy sample showed [111In]In-DOTA-JR11 uptake at plaque locations containing CD68 and SST2 expressing cells.

Conclusions

The results of this study indicate DOTA-JR11 as a promising ligand for visualization of atherosclerotic plaque inflammation.

SUBMITTER: Meester EJ 

PROVIDER: S-EPMC8709817 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Imaging inflammation in atherosclerotic plaques, targeting SST<sub>2</sub> with [<sup>111</sup>In]In-DOTA-JR11.

Meester Eric J EJ   Krenning Boudewijn J BJ   de Blois Erik E   de Jong Marion M   van der Steen Antonius F W AFW   Bernsen Monique R MR   van der Heiden Kim K  

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 20200205 6


<h4>Background</h4>Imaging Somatostatin Subtype Receptor 2 (SST<sub>2</sub>) expressing macrophages by [DOTA,Tyr<sup>3</sup>]-octreotate (DOTATATE) has proven successful for plaque detection. DOTA-JR11 is a SST<sub>2</sub> targeting ligand with a five times higher tumor uptake than DOTATATE, and holds promise to improve plaque imaging. The aim of this study was to evaluate the potential of DOTA-JR11 for plaque detection.<h4>Methods and results</h4>Atherosclerotic ApoE<sup>-/-</sup> mice (n = 22)  ...[more]

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