Sire Charline, Meneyrol Vincent, Saffon-Merceron Nathalie, Terreno Enzo, Garello Francesca, Tei Lorenzo, Jestin Emmanuelle, Tripier Raphaël, Troadec Thibault
Univ. Brest, UMR CNRS 6521 CEMCA 6 Avenue Victor Le Gorgeu 29200 Brest France
Cyclotron Réunion Océan Indien CYROI 2 rue Maxime Rivière 97490 Sainte-Clotilde France.
Chem Sci. 2024 Jul 25;15(33):13550-13557. doi: 10.1039/d4sc02871f. eCollection 2024 Aug 22.
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 F for Positron Emission Tomography (PET) or natural 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 F-PET or F MRI abilities provided by this novel molecular structure. The chelator and the complex were obtained a simple and high-yielding synthetic route, present excellent solvolytic stability of the trifluoroborate groups at various pH, and provide facile late-stage F-radiolabeling (up to 68% radiochemical yield with high activity) as well as a satisfying detection limit for F MRI imaging (low mM range).
大环螯合剂因其无与伦比的金属阳离子配位能力，在医学成像和核医学中发挥着核心作用。通过氟化基团对其进行功能化是一种有吸引力的设计，可将它们的特性与用于正电子发射断层扫描（PET）的氟或用于磁共振成像（MRI）的天然氟的特性相结合，从而获得潜在的诊疗一体化或智能医学成像探针。首次基于带有额外吡啶配位单元和简单甲基三氟硼酸盐基团的轮环配体螯合剂，合成了一种紧凑的氟化大环结构。对该配体及其相应的模型锌（II）配合物进行了研究，以评估这种新型分子结构所提供的氟-正电子发射断层扫描（F-PET）或氟磁共振成像（F-MRI）能力。该螯合剂和配合物通过简单且高产率的合成路线获得，在不同pH值下三氟硼酸盐基团具有出色的溶剂分解稳定性，并且提供便捷的后期氟放射性标记（放射性化学产率高达68%，活性高）以及令人满意的氟磁共振成像检测限（低毫摩尔范围）。
