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PFKFB3, a glycolysis-related enzyme upregulated in inflammatory conditions and angiogenesis, is an emerging target for diagnosis and therapy of atherosclerosis. The fluorinated phenoxindazole [ 18 F] ZCDD083 was synthesized, radiolabeled in 17 ± 5% radiochemical yield and &gt;99% radiochemical purity, and formulated for preclinical 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 postinjection (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 [ 18 F] ZCDD083 in the arch region and brachiocephalic artery of atherosclerotic mice, and no uptake in control mice, matching plaques distribution seen by lipid staining along with PFKFB3 expression seen by immunofluorescent staining. In vivo PET scans showed higher aortic region uptake of [ 18 F] ZCDD083 in atherosclerotic ApoE -/- Fbn1 C1039G+/- than in control mice (0.78 ± 0.05 vs 0.44 ± 0.09%ID/g). [ 18 F] ZCDD083 was detected in aortic arch and brachiocephalic artery of ApoE -/- (with moderate atherosclerosis) and ApoE -/- Fbn1 C1039G+/- (with severe, advanced atherosclerosis) mice, suggesting this tracer may be useful for the noninvasive detection of atherosclerotic plaques in vivo .

[18F]ZCDD083: A PFKFB3-Targeted PET Tracer for Atherosclerotic Plaque Imaging

[¹⁸F]ZCDD083: A PFKFB3-Targeted PET Tracer for Atherosclerotic Plaque Imaging