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Macrocyclic chelators play a central role in medical imaging and nuclear medicine owing to their unparalleled metal cation coordination abilities. Their functionalization by fluorinated groups is an attractive design, to combine their properties with those of 18 F for Positron Emission Tomography (PET) or natural 19 F for Magnetic Resonance Imaging (MRI), and access potential theranostic or smart medical imaging probes. For the first time, a compact fluorinated macrocyclic architecture has been synthesized, based on a cyclen chelator bearing additional pyridine coordinating units and simple methyltrifluoroborate prosthetic groups. This ligand and its corresponding model Zn(ii) complex were investigated to evaluate the 18 F-PET or 19 F MRI abilities provided by this novel molecular structure. The chelator and the complex were obtained via a simple and high-yielding synthetic route, present excellent solvolytic stability of the trifluoroborate groups at various pH, and provide facile late-stage 18 F-radiolabeling (up to 68% radiochemical yield with high activity) as well as a satisfying detection limit for 19 F MRI imaging (low mM range)., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Atherosclerosis and its associated clinical complications are major health issues in industrialized countries. Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) was demonstrated to play an important role in atherogenesis and to be a potential risk prediction factor of plaque rupture. Darapladib is one of the most potent Lp-PLA 2 inhibitors with an IC 50 of 0.25 nM. Using its affinity for Lp-PLA 2 , we describe herein the total synthesis of darapladib radiolabeling precursor and the automated radiolabeling process for positron emission tomography (PET) imaging via an arylboronate moiety. The tracer thus obtained was tested in a mouse model of atherosclerosis (ApoE KO) and compared with the widely used [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) PET tracer, known to label metabolically active cells. [ 18 F]Darapladib showed a significant accumulation within mice aortic atheromatous plaques dissected out ex vivo compared to [ 18 F]FDG. Incubation of the radiotracer with human carotid samples showed a strong accumulation within the atherosclerotic plaques and supports its potential for use in PET imaging., Competing Interests: The authors declare no competing financial interest.