Evaluation of [99mTc]Radiolabeled Macrophage Mannose Receptor-Specific Nanobodies for Targeting of Atherosclerotic Lesions in Mice

Abstract

No significant uptake of MMR-specific Nb could be observed in atherosclerotic lesions of ApoE mice in this study. A specific perivascular signal causing a non-negligible background level was demonstrated. This observation should be considered when using MMR as a target in molecular imaging of atherosclerosis, as well as use of translational animal models with vulnerable plaques.

Nanobody-Facilitated Multiparametric PET/MRI Phenotyping of Atherosclerosis

“…However, whereas in rabbits there was no clear difference among aortic 64 Cu-nanobody up-takes, in Apoe –/– mice 64 Cu-MMR uptake was significantly higher. Although this uptake can be attributed in part to MMR-positive cells in the adventitial layer and the surrounding perivascular tissue of atherosclerotic lesions of Apoe –/– mice ( 23 ), in rabbits we did observe an increased plaque up-take compared to control subjects and expression of the mannose receptor within the lesions. These observations likely reflect the differences in lesion composition between the 2 models ( 24 ).…”

Targeting mannose receptor expression on macrophages in atherosclerotic plaques of apolipoprotein E-knockout mice using 68Ga-NOTA-anti-MMR nanobody: non-invasive imaging of atherosclerotic plaques

“…In the previous study, we were not able to evaluate the relevance of the technetium-99m ( 99m Tc)-labelled anti-MMR3.49 Nb for atherosclerosis and no positive correlation was found between plaque burden and 99m Tc-anti-MMR3.49 Nb uptake. As confirmed by immunofluorescence staining, the absence of 99m Tc-anti-MMR3.49 Nb uptake in the plaques corroborated with the absence of MR expression in the lesions [36]. However, we warned for MR expression in the adventitial tissue.…”

Targeted Nanobody-Based Molecular Tracers for Nuclear Imaging and Image-Guided Surgery

“…Applications that heavily rely on an elevated uptake with low nonspecific surrounding background signals are the imaging of pancreatic islets after transplantation [83] and the imaging of vulnerable atherosclerotic plaques. The feasibility to noninvasively detect small, inflamed atherosclerotic lesions in the aortic arch of mice or along the aortas of atherosclerotic rabbits has been shown with radiolabeled nanobodies targeting MMR, vascular cell adhesion molecule-1 (VCAM-1) (Figure 1E), and lectin-like oxidized low-density lipoprotein receptor (LOX-1) [43,52,84,85,86,87,88,89]. However, their prognostic value for the identification of high-risk patients remains to be demonstrated in clinical trials.…”