[18F]ZCDD083: a PFKFB3-targeted PET tracer for atherosclerotic plaque imaging

Carlo De Dominicis, Paola Perrotta, Sergio Dall'angelo, Leonie Wyffels, Steven Staelens, G. R. Y. de Meyer, Matteo Zanda

Research output: Contribution to journalArticle

Abstract

PFKFB3, a glycolysis-related enzyme upregulated in inflammatory conditions and angiogenesis, is an emerging target for diagnosis and therapy of atherosclerosis. The fluorinated phenoxindazole [18F]ZCDD083 was synthesised, 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. Biodistribution studies showed high blood pool activity and slow hepatobiliary clearance. Significant activity was detected in the lung 2 h post-injection (pi) (11.0 ±1.5 %ID/g), while at 6 h pi no pulmonary background was observed. 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, match-ing plaques distribution 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.
Original languageEnglish
JournalACS Medicinal Chemistry Letters
Early online date24 Feb 2020
DOIs
Publication statusE-pub ahead of print - 24 Feb 2020

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