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.

Additional Metadata
Keywords atherosclerosis, inflammation, molecular imaging, SPECT
Persistent URL dx.doi.org/10.1007/s12350-020-02046-y, hdl.handle.net/1765/124713
Journal Journal of Nuclear Cardiology
Citation
Meester, E.J. (Eric J.), Krenning, B.J, de Blois, E, de Jong, M. (Marion), van der Steen, A.F.W, Bernsen, M.R, & van der Heiden, K. (2020). Imaging inflammation in atherosclerotic plaques, targeting SST2 with [111In]In-DOTA-JR11. Journal of Nuclear Cardiology. doi:10.1007/s12350-020-02046-y