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

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.