Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging

Molecules

Benedicte Descamps¹  Christian Vanhove¹  Nick Devoogdt²  Catarina Xavier²  Pieterjan Debie²  Jessica Bridoux²  Sophie Hernot²  Vicky Caveliers²  Sara Neyt³  Guy Bormans⁴  Frederik Cleeren⁴  Alexis Broisat⁵ 

[1] IBiTech-MEDISIP, Ghent University, 9000 Ghent, Belgium;Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium;Preclinical imaging, MOLECUBES NV, 9000 Ghent, Belgium;Radiopharmaceutical Research, KU Leuven, 3000 Leuven, Belgium;Radiopharmaceutiques Biocliniques, INSERM 1039, Université de Grenoble, 38400 Grenoble, France;

关键词: vulnerable plaque;    molecular imaging;    PET imaging;    nanobody;    single-domain antibody;    sub-millimetre resolution;   

DOI  :  10.3390/molecules25081838

来源: DOAJ

【 摘 要 】

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 [¹⁸F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [¹⁸F]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 [¹⁸F]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 β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.

【 授权许可】

Unknown