期刊
MOLECULES
卷 25, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/molecules25081838
关键词
vulnerable plaque; molecular imaging; PET imaging; nanobody; single-domain antibody; sub-millimetre resolution; AlF-radiolabelling
资金
- FWO project [G005815N, G0D8817N]
- Scientific Fund W. Gepts UZ Brussel
- EU H2020 MSCA ITN PET3D
- FWO [12R3119N]
Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [F-18]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [F-18]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE(-/-) mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET /CT images and ex vivo data showed specific uptake of [F-18]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the beta-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.
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