Published April 16, 2020 | Version v1
Journal article Open

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

  • 1. Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
  • 2. Preclinical imaging, MOLECUBES NV, 9000 Ghent, Belgium
  • 3. IBiTech-MEDISIP, Ghent University, 9000 Ghent, Belgium
  • 4. Radiopharmaceutical Research, KU Leuven, 3000 Leuven, Belgium
  • 5. Radiopharmaceutiques Biocliniques, INSERM 1039, Université de Grenoble, 38400 Grenoble, France
  • 6. Nuclear Medicine department, UZ Brussel, 1090 Brussels, Belgium; Laboratory of In Vivo Cellular and Molecular Imaging (ICMI, BEFY-MIMA), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium

Description

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 -CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.

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Additional details

Funding

European Commission
PET3D – PET Imaging in Drug Design and Development 675417