Corot C, Idee J M, Hentsch A M, Santus R, Mallet C, Goulas V, Bonnemain B, Meyer D
Biochemistry Department, Laboratoire Guerbet, Aulnay Sous Bois, France.
J Magn Reson Imaging. 1998 May-Jun;8(3):695-702. doi: 10.1002/jmri.1880080328.
Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylenetriamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC50 = .016 +/- .006 mmol/l) and Gd-DTPA (IC50 = .350 +/- .034 mmol/l). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn2+ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: (67 +/- 9% versus baseline; and Gd-DTPA-BMA: 73 +/- 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd3+ release) in the case of linear Gd chelate may have deleterious biologic consequences.
研究了市售钆（Gd）螯合物溶液与锌（Zn）依赖性血管紧张素转换酶（ACE）之间的金属转移反应。在体外，观察到线性Gd络合物钆二乙烯三胺五乙酸（DTPA）双甲酰胺（BMA）（IC50 = 0.016±0.006 mmol/L）和钆-DTPA（IC50 = 0.350±0.034 mmol/L）具有最强的抑制作用。两种大环化合物钆四氮杂环十二烷四乙酸（DOTA）和钆-HP-DO3A的活性相似，且比钆-DTPA-BMA低400倍。这些作用主要归因于DTPA存在游离配体以及DTPA-BMA存在钙（Ca）螯合物，因为加入等量的Zn2+可抑制它们的抑制作用。在体内，这两种线性Gd螯合物溶液显著抑制ACE活性（临床剂量为0.1 mmol/kg时，钆-DTPA：与基线相比为67±9%；钆-DTPA-BMA：与基线相比为73±2%），而两种大环螯合物钆-DOTA和钆-HP-DO3A未观察到显著作用。对于线性Gd螯合物，用过量的游离配体或Ca螯合物配制Gd螯合物溶液（以减少Gd3+释放）可能会产生有害的生物学后果。
