Abstract
BackgroundImaging 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 ResultsAtherosclerotic 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. ConclusionsThe results of this study indicate DOTA-JR11 as a promising ligand for visualization of atherosclerotic plaque inflammation.
Highlights
Cardiovascular disease is the leading cause of death worldwide.[1]
Atherosclerotic ApoE2/2 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)
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 Somatostatin Subtype Receptor 2 (SST2) expressing cells
Summary
Cardiovascular disease is the leading cause of death worldwide.[1] Most cardiovascular events are caused by atherosclerosis, in which plaques form over time due to continuous inflammation and lipid deposition in the arterial wall. Imaging plaque inflammation may complement traditional imaging methods, providing a better risk stratification of patients at risk of future cardiovascular events. 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has proven a reliable non-invasive imaging method to detect, but even to quantify the degree of inflammation in plaques.5–7 18F-FDG, provides a valuable tool to assess and monitor disease burden.[8]. Imaging Somatostatin Subtype Receptor 2 (SST2) expressing macrophages by [DOTA,Tyr3]-octreotate (DOTATATE) has proven successful for plaque detection. DOTAJR11 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
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