Dioury Fabienne, San Carine, Gnanalingam Gayathiri, Henoumont Céline, Rousselin Yoann, Haouz Ahmed, Shepard William, Hosten Benoît, Vijayakumar Kamsana, Laurent Sophie, Port Marc
Conservatoire national des arts et métiers, Laboratoire Génomique, bioinformatique et chimie moléculaire (GBCM), EA 7528, 2 rue Conté, 75003, Paris, France.
Hôpital Saint-Louis, Université Paris Cité, Institut de Recherche Saint-Louis, Unité Claude Kellershohn, 1 avenue Claude Vellefaux, 75010, Paris, France.
Chemistry. 2024 Dec 5;30(68):e202403358. doi: 10.1002/chem.202403358. Epub 2024 Nov 9.
Positron Emission Tomography (PET) is used in oncology for tumor diagnosis, commonly relying on fluorine-18 (F) emission detection. The conventional method of F incorporation on to probes by covalent bonding is harsh for sensitive biomolecules, which are nonetheless compounds of choice for the development of targeted probes. This study explores gallium-F (GaF) coordination, a milder alternative method occurring in aqueous media at the final stage of radiosyntheses. Pyclen-based chelating agents were proposed to capture (GaF) species at room temperature and pH≥5 making the radiofluorination process compatible with heat- and acid-sensitive biomolecules. Highly promising results were obtained with the PC2A-based chelating agent LH derived from the new bifunctional PC2A-OAE-NCS compound. The solid-state structure of GaF(L) was elucidated by X-ray diffraction and revealed an unconventional heptacoordination of Ga(III). A high radiochemical conversion (RCC) of 86 % was achieved at room temperature, in water at pH 5 within 20 minutes. Stability studies showed the robustness of the GaF(L) complex in aqueous media for at least one day and at least one hour for the radiolabeled analog GaF(L). These findings demonstrated that PC2A-based compounds are chelating agents of choice for (GaF) species, suggesting a real technological breakthrough for PET imaging and precision medicine.
正电子发射断层扫描（PET）在肿瘤学中用于肿瘤诊断，通常依靠检测氟-18（F）发射。通过共价键将F结合到探针上的传统方法对敏感生物分子来说较为苛刻，而这些生物分子却是开发靶向探针的首选化合物。本研究探索了镓-F（GaF）配位，这是一种在放射性合成最后阶段在水性介质中发生的较为温和的替代方法。有人提出基于Pyclen的螯合剂在室温及pH≥5的条件下捕获（GaF）物种，使放射性氟化过程与对热和酸敏感的生物分子兼容。从新型双功能PC2A-OAE-NCS化合物衍生而来的基于PC2A的螯合剂LH取得了非常有前景的结果。通过X射线衍射阐明了GaF（L）的固态结构，揭示了Ga（III）的非常规七配位。在室温下，于pH 5的水中20分钟内实现了86%的高放射化学转化率（RCC）。稳定性研究表明，GaF（L）配合物在水性介质中至少稳定一天，而放射性标记类似物GaF（L）至少稳定一小时。这些发现表明，基于PC2A的化合物是捕获（GaF）物种的首选螯合剂，这为PET成像和精准医学带来了真正的技术突破。
