Fiaccabrino Desiree, Masvikeni Tinotenda, Jaraquemada-Peláez María de Guadalupe, Orvig Chris, Schaffer Paul
Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia ,V6T 1Z1, Canada.
Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia ,V6T 2A3, Canada.
Inorg Chem. 2024 Jul 29;63(30):13911-13923. doi: 10.1021/acs.inorgchem.4c01180. Epub 2024 Jul 16.
Htrica is a nonadentate chelating ligand intended for coordinating large radiometal ions, such as those used in nuclear medicine. This chelator, featuring a triaza-18-crown-6 macrocycle with three pendant carboxylic acid functional groups, was synthesized and characterized. Complementary nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray-ionization mass spectroscopy (HR-ESI-MS) studies were used to explore the coordination of Htrica with metal ions such as La, Y (as a model for Tb, and Lu at the bulk scale. Thermodynamic solution studies provided valuable insights, highlighting robust metal complexation of Htrica with La, Tb, and Lu, with the most noteworthy log value observed for Tb (log = 17.08), followed by La (log = 16.64) and Lu (log = 16.25). Concentration-dependent radiolabeling studies with [Ac]Ac, [Tb]Tb, and [Tb]Tb demonstrated rapid complexation (5-30 min) under mild conditions (pH 6-7, 25 °C). Importantly, the radiolabeled complexes exhibited stability during incubation in human serum for one-half-life of the corresponding radiometal. Thus, Htrica emerges as a valuable chelator, demonstrating its potential to coordinate the theranostic couple [Ac]Ac/[Tb]Tb as well as the powerful terbium quartet ([Tb]Tb) with efficiency and stability.
Htrica是一种非齿状螯合配体，旨在配位大型放射性金属离子，如核医学中使用的那些离子。合成并表征了这种螯合剂，它具有一个带有三个羧酸侧基官能团的三氮杂-18-冠-6大环。利用互补的核磁共振（NMR）光谱和高分辨率电喷雾电离质谱（HR-ESI-MS）研究来探索Htrica与诸如La、Y（作为Tb和Lu在宏观尺度上的模型）等金属离子的配位情况。热力学溶液研究提供了有价值的见解，突出了Htrica与La、Tb和Lu的强金属络合作用，其中观察到Tb的log 值最为显著（log = 17.08），其次是La（log = 16.64）和Lu（log = 16.25）。用[Ac]Ac、[Tb]Tb和[Tb]Tb进行的浓度依赖性放射性标记研究表明，在温和条件下（pH 6 - 7，25°C）能快速络合（5 - 30分钟）。重要的是，放射性标记的络合物在人血清中孵育时，对于相应放射性金属的半衰期表现出稳定性。因此，Htrica成为一种有价值的螯合剂，证明了其有效且稳定地配位治疗诊断对[Ac]Ac/[Tb]Tb以及强大的铽四重态（[Tb]Tb）的潜力。
