Department of Science and Technological Innovation, Università del Piemonte Orientale, Viale T. Michel 11, 15121 Alessandria, Italy.
Bracco Research Centre, Bracco Imaging S.p.A., Via Ribes 5, 10010 Colleretto Giacosa, Italy.
Molecules. 2023 Apr 27;28(9):3764. doi: 10.3390/molecules28093764.
Al(III) complexes have been recently investigated for their potential use in imaging with positron emission tomography (PET) by formation of ternary complexes with the radioisotope fluorine-18 (F). Although the derivatives of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) are the most applied chelators for [AlF] labelling and (pre)clinical PET imaging, non-macrocyclic, semi-rigid pentadentate chelators having two N- and three O-donor atoms such as RESCA1 and AMPDA-HB have been proposed with the aim to allow room temperature labelling of temperature-sensitive biomolecules. The paucity of stability data on Al(III) complexes used for PET imaging instigated a complete thermodynamic and kinetic solution study on Al(III) complexes with aminomethylpiperidine (AMP) derivatives AMPTA and AMPDA-HB and the comparison with a RESCA1-like chelator CD3A-Bn (-1,2-diaminocyclohexane--benzyl-,,-triacetic acid). The stability constant of [Al(AMPDA-HB)] is about four orders of magnitude higher than that of [Al(AMPTA)] and [Al(CD3A-Bn)], highlighting the greater affinity of phenolates with respect to acetate O-donors. On the other hand, the kinetic inertness of the complexes, determined by following the Cu-mediated transmetallation reactions in the 7.5-10.5 pH range, resulted in a spontaneous and hydroxide-assisted dissociation slightly faster for [Al(AMPTA)] than for the other two complexes ( = 4.5 h for [Al(AMPTA)], 12.4 h for [Al(AMPDA-HB)], and 24.1 h for [Al(CD3A-Bn)] at pH 7.4 and 25 °C). Finally, the [AlF] ternary complexes were prepared and their stability in reconstituted human serum was determined by F NMR experiments.
铝（III）配合物最近因其与放射性同位素氟-18（F）形成三元配合物的潜力而被用于正电子发射断层扫描（PET）成像的研究。虽然 1,4,7-三氮杂环壬烷-1,4,7-三乙酸（NOTA）的衍生物是用于[AlF]标记和（临床前）PET 成像的最应用螯合剂，但具有两个 N 和三个 O 供体原子的非大环、半刚性五齿螯合剂，如 RESCA1 和 AMPDA-HB，已被提出，旨在允许对温度敏感的生物分子进行室温标记。用于 PET 成像的铝（III）配合物的稳定性数据不足促使对具有氨基甲基哌啶（AMP）衍生物 AMPTA 和 AMPDA-HB 的铝（III）配合物进行了全面的热力学和动力学溶液研究，并与类似 RESCA1 的螯合剂 CD3A-Bn（-1,2-二氨基环己烷--苄基，-，-三乙酸）进行了比较。[Al（AMPDA-HB）]的稳定常数比[Al（AMPTA）]和[Al（CD3A-Bn）]高约四个数量级，这突出了酚盐相对于乙酸 O 供体的更高亲和力。另一方面，通过在 7.5-10.5 pH 范围内跟踪 Cu 介导的转金属反应来确定配合物的动力学惰性，结果表明[Al（AMPTA）]的自发和氢氧化物辅助解离略快于其他两个配合物（在 pH 7.4 和 25°C 时，[Al（AMPTA）]的 = 4.5 h，[Al（AMPDA-HB）]的 12.4 h，[Al（CD3A-Bn）]的 24.1 h）。最后，制备了[AlF]三元配合物，并通过 F NMR 实验确定了它们在重组人血清中的稳定性。
