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- Title
Imaging inflammation in atherosclerotic plaques, targeting SST<sub>2</sub> with [<sup>111</sup>In]In-DOTA-JR11.
- Authors
Meester, Eric J.; Krenning, Boudewijn J.; de Blois, Erik; de Jong, Marion; van der Steen, Antonius F. W.; Bernsen, Monique R.; van der Heiden, Kim
- 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.
- Subjects
ATHEROSCLEROTIC plaque; STAINS &; staining (Microscopy); CAROTID endarterectomy; SOMATOSTATIN receptors; AUTORADIOGRAPHY
- Publication
Journal of Nuclear Cardiology, 2021, Vol 28, Issue 6, p2506
- ISSN
1071-3581
- Publication type
Article
- DOI
10.1007/s12350-020-02046-y