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.
De Dominicis, C., Perrotta, P., Dall'angelo, S., Wyffels, L., Staelens, S., de Meyer, G. R. Y., & Zanda, M. (2020). [18F]ZCDD083: a PFKFB3-targeted PET tracer for atherosclerotic plaque imaging. ACS Medicinal Chemistry Letters. https://doi.org/10.1021/acsmedchemlett.9b00677