[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

doi:10.1021/acsmedchemlett.9b00677

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

ACS Med Chem Lett. 2020 Feb 19;11(5):933-939. doi: 10.1021/acsmedchemlett.9b00677. eCollection 2020 May 14.

Authors

Carlo De Dominicis¹, Paola Perrotta², Sergio Dall'Angelo¹, Leonie Wyffels³, Steven Staelens³, G R Y De Meyer², Matteo Zanda^{1

4}

Affiliations

¹ Kosterlitz Centre for Therapeutics, University of Aberdeen, AB25 2ZD Foresterhill, Aberdeen, U.K.
² Laboratory of Physiopharmacology, University of Antwerp, 2610 Antwerpen, Belgium.
³ Molecular Imaging Center Antwerp, University of Antwerp, 2610 Antwerpen, Belgium.
⁴ CNR-ICRM, via Mancinelli 7, 20131 Milan, Italy.

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 synthesized, radiolabeled in 17 ± 5% radiochemical yield and >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 [¹⁸F]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 [¹⁸F]ZCDD083 in atherosclerotic ApoE^-/-Fbn1^C1039G+/- 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^-/-Fbn1^C1039G+/- (with severe, advanced atherosclerosis) mice, suggesting this tracer may be useful for the noninvasive detection of atherosclerotic plaques in vivo.