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

• Published in: Journal of nuclear cardiology 2021-12, Vol.28 (6), p.2506-2513
• Main 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
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Cardiology; Imaging; inflammation; Ligands; Medicine; Medicine & Public Health; molecular imaging; Nuclear Medicine; Original; Original Article; Radiology; SPECT
• ISSN: 1071-3581; 1532-6551
• DOI: 10.1007/s12350-020-02046-y

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