Zanda Manuscript ACS Medicinal Chemistry Letters no template_Final revised (2).pdf (786.37 kB)
[18F]ZCDD083: A PFKFB3-Targeted PET Tracer for Atherosclerotic Plaque Imaging
journal contribution
posted on 2020-06-04, 10:50 authored by Carlo De Dominicis, Paola Perrotta, Sergio Dall’Angelo, Leonie Wyffels, Steven Staelens, GRY De Meyer, Matteo Zanda: PFKFB3, a glycolysis-related enzyme upregulated in inflammatory conditions and angiogenesis, is an emerg-ing target for diagnosis and therapy of atherosclerosis. The fluorinated phenoxindazole [18F]ZCDD083 was syn-thesised, radiolabelled in 17 ±5% radiochemical yield and >99% radiochemical purity, and formulated for pre-clinical PET/CT imaging in mice. In vivo stability analysis showed no significant metabolite formation. Biodistri-bution studies showed high blood pool activity and slow hepatobiliary clearance. Significant activity was de-tected in the lung 2 h post-injection (pi) (11.0 ±1.5 %ID/g), while at 6 h pi no pulmonary background was ob-served. Ex vivo autoradiography at 6 h pi showed significant high uptake of [18F]ZCDD083 in the arch region and brachiocephalic artery of atherosclerotic mice, and no uptake in control mice, matching plaques distribu-tion seen by lipid staining along with PFKFB3 expression seen by immunofluorescent staining. In vivo PET scans showed higher aortic region uptake of [18F]ZCDD083 in atherosclerotic ApoE-/-Fbn1C1039G+/- than in control mice (0.78 ± 0.05 vs 0.44 ± 0.09 %ID/g). [18F]ZCDD083 was detected in aortic arch and brachiocephalic artery of ApoE-/- (with moderate atherosclerosis) and ApoE-/-Fbn1C1039G+/- (with severe, advanced atherosclerosis) mice, suggesting this tracer may be useful for the non-invasive detection of atherosclerotic plaques in vivo.
Funding
European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie ITN-European Joint Doctorate MOGLYNET (grant agreement No. 675527).
History
School
- Science
Department
- Computer Science
Published in
ACS Medicinal Chemistry LettersVolume
11Issue
5Pages
933 - 939Publisher
American Chemical Society (ACS)Version
- AM (Accepted Manuscript)
Rights holder
© American Chemical SocietyPublisher statement
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsmedchemlett.9b00677Acceptance date
2020-02-19Publication date
2020-02-19Copyright date
2020ISSN
1948-5875eISSN
1948-5875Publisher version
Language
- en