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

Background Imaging Somatostatin Subtype Receptor 2 (SST2) expressing macrophages by [DOTA,Tyr(3)]-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 [In-111]In-DOTA-JR11 (similar to 200 pmol, similar to 50 MBq). In vivo plaque uptake of [In-111]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 [In-111]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 [In-111]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.

Automated summary

The study demonstrated DOTA-JR11 as a promising ligand for visualization of atherosclerotic plaque inflammation. In vivo and post-mortem scans showed plaque uptake of [In-111]In-DOTA-JR11 with high target-to-background ratios. Histological processing confirmed the presence of CD68 and SST2 expressing cells in plaques.