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. 2024 Mar-Apr:130-131:108893.
doi: 10.1016/j.nucmedbio.2024.108893. Epub 2024 Feb 23.

Development of a CCR2 targeted 18F-labeled radiotracer for atherosclerosis imaging with PET

Xiaohui Zhang  1 , Lin Qiu  1 , Debbie H Sultan  1 , Hannah P Luehmann  1 , Yanbo Yu  1 , Xiuli Zhang  1 , Gyu Seong Heo  1 , Alexandria Li  1 , Divangana Lahad  1 , Shinji Rho  2 , Zhude Tu  1 , Yongjian Liu  3
Affiliations

Development of a CCR2 targeted 18F-labeled radiotracer for atherosclerosis imaging with PET

Xiaohui Zhang et al. Nucl Med Biol. 2024 Mar-Apr.

Abstract

Atherosclerosis is a chronic inflammatory disease and the leading cause of morbidity and mortality worldwide. CC motif chemokine ligand 2 and its corresponding cognate receptor 2 (CCL2/CCR2) signaling has been implicated in regulating monocyte recruitment and macrophage polarization during inflammatory responses that plays a pivotal role in atherosclerosis initiation and progression. In this study, we report the design and synthesis of a novel 18F radiolabeled small molecule radiotracer for CCR2-targeted positron emission tomography (PET) imaging in atherosclerosis. The binding affinity of this radiotracer to CCR2 was evaluated via in vitro binding assay using CCR2+ membrane and cells. Ex vivo biodistribution was carried out in wild type mice to assess radiotracer pharmacokinetics. CCR2 targeted PET imaging of plaques was performed in two murine atherosclerotic models. The sensitive detection of atherosclerotic lesions highlighted the potential of this radiotracer for CCR2 targeted PET and warranted further optimization.

Keywords: (18)F radiolabeling; Atherosclerosis; CCR2; Macrophages; PET/CT.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
Synthetic route of the precursor SMCCR2-OH and the standard compound SMCCR2-F.
Fig. 2.
Fig. 2.
(A) Synthetic route of SMCCR2-18F. (B) HPLC profiles of precursor SMCCR2-OH, non-radiolabeled standard SMCCR2-F, and radiotracer SMCCR2-18F. (C) HPLC of SMCCR2-18F in mouse serum at 3 hrs.
Fig. 3.
Fig. 3.
Competitive binding assay of SMCCR2-18F using CCR2 membrane and THP-1 cells.
Fig. 4.
Fig. 4.
Biodistribution of SMCCR2-18F in WT mice at 1 h post injection (n=4).
Fig. 5.
Fig. 5.
Representative PET/CT images (A) and quantitative analysis and plaque to adjacent heart muscle ratios (B) of SMCCR2-18F, SMCCR2-18F blocked with 500 times non-radiolabeled standard SMCCR2-F in ApoE−/− mice with average 36-week HFD and SMCCR2-18F in wild type control mice. (C) H&E and CCR2 immunofluorescence staining of the mouse aorta.
Fig. 6.
Fig. 6.
Representative PET/CT images (A) and quantitative analysis and plaque to adjacent heart muscle ratios (B) of SMCCR2-18F and co-injected with 500 times non-radiolabeled standard SMCCR2-F in 32-week-old PCSK9 mice.
Fig. 7.
Fig. 7.
Ex vivo characterization of human CEA specimen showing abundant CCR2+ cells in the plaque in aorta.
See this image and copyright information in PMC

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