Farkas Edit, Nagel Johannes, Waldron Bradley P, Parker David, Tóth Imre, Brücher Ernő, Rösch Frank, Baranyai Zsolt
Department of Inorganic and Analytical Chemistry, University of Debrecen, Egyetem tér 1, 4032, Debrecen, Hungary.
Institute of Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, 55128, Mainz, Germany.
Chemistry. 2017 Aug 1;23(43):10358-10371. doi: 10.1002/chem.201701508. Epub 2017 Jul 12.
The development of Ge/ Ga generators has made the positron-emitting Ga isotope widely accessible and raised interest in new chelate complexes of Ga . The hexadentate 1,4-di(acetate)-6-methyl[amino(methyl)acetate]perhydro-1,4-diazepane (DATA ) ligand and its bifunctional analogue, 1,4-di(acetate)-6-pentanoic acid[amino(methyl)acetate]perhydro-1,4-diazepane (DATA ), rapidly form complexes with Ga in high radiochemical yield. The stability constants of DATA and DATA complexes formed with Ga , Zn , Cu , Mn and Ca have been determined by using pH potentiometry, spectrophotometry (Cu ) and H and Ga NMR spectroscopy (Ga ). The stability constants of Ga(DATA ) and Ga(DATA ) complexes are slightly higher than those of Ga(AAZTA). The species distribution calculations indicated the predominance of Ga(L)OH mixed-hydroxo complexes at physiological pH. The H and Ga NMR spectroscopy studies provided information about the coordinated functional groups of ligands and on the kinetics of exchange between the Ga(L) and Ga(L)OH complexes. The transmetalation reactions between the Ga(L) complexes and Cu citrate (6<pH<8.5) occur through both spontaneous and OH -assisted dissociation of the Ga(L)OH species. At pH 7.4 and 25 °C, the half-lives of the dissociation of Ga(DATA ), Ga(DATA ) and Ga(AAZTA) were 11, 44 and 24 h, respectively. Similar half-lives have been obtained for the ligand-exchange reactions between the Ga(L)OH complexes and transferrin. The equilibrium and kinetic data indicate that the Ga(DATA ) complex is a good Ga-based radiodiagnostic candidate.
锗/镓发生器的发展使得发射正电子的镓同位素广泛可得，并引发了人们对新型镓螯合物的兴趣。六齿配体1,4 - 二（乙酸酯）- 6 - 甲基[氨基（甲基）乙酸酯]全氢 - 1,4 - 二氮杂环庚烷（DATA）及其双功能类似物1,4 - 二（乙酸酯）- 6 - 戊酸[氨基（甲基）乙酸酯]全氢 - 1,4 - 二氮杂环庚烷（DATA）能以高放射化学产率迅速与镓形成配合物。通过pH电位滴定法、分光光度法（铜）以及氢和镓核磁共振光谱法（镓）测定了DATA和DATA与镓、锌、铜、锰和钙形成的配合物的稳定常数。镓（DATA）和镓（DATA）配合物的稳定常数略高于镓（AAZTA）的稳定常数。物种分布计算表明在生理pH值下镓（L）OH混合羟基配合物占主导。氢和镓核磁共振光谱研究提供了有关配体配位官能团以及镓（L）和镓（L）OH配合物之间交换动力学的信息。镓（L）配合物与柠檬酸铜之间的转金属化反应（6 < pH < 8.5）通过镓（L）OH物种的自发解离和OH - 辅助解离两种方式发生。在pH 7.4和25℃时，镓（DATA）、镓（DATA）和镓（AAZTA）解离的半衰期分别为11、44和24小时。对于镓（L）OH配合物与转铁蛋白之间的配体交换反应也获得了类似的半衰期。平衡和动力学数据表明镓（DATA）配合物是一种良好的基于镓的放射诊断候选物。
