Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi-110054, India.
Chem Biol Drug Des. 2011 May;77(5):388-92. doi: 10.1111/j.1747-0285.2011.01103.x. Epub 2011 Mar 25.
Diethlenetriamine-N,N,N'N''N''-pentaacetic acid (DTPA)-bis (amide) analogs have been synthesized and evaluated as a potential biomedical imaging agents. Imaging and biodistribution studies were performed in mice that showed a significant accumulation of DTPA analogs in brain. The stability and protonation constants of the complexes formed between the ligand [DTPA-(Me-Trp)(2)] and Gd(3+), Eu(3+), and Cu(2+) have been determined by pH potentiometry (Gd(3+), Eu(3+)) and spectrophotometry (Cu(2+)) at 25 °C and at constant ionic strength maintained by 0.10 M KCl. The kinetic inertness of Gd [DTPA-(Me-Trp)(2)] was characterized by the rates of exchange reactions with Zn(2+) and Eu(3+). In the Eu(3+) exchange, a second-order [H(+)] dependence was found for the pseudo-first-order rate constant [k(0) = (4.5 ± 1.2) × 10(-6)/s; k(1) = 0.58 ± 0.1 /M/s, k(2) = (6.6 ± 0.2) × 10(4) /M(2)/s, k(3) = (4.8 ± 0.8) × 10(-4) /M/s]. In the Eu(3+) exchange, at pH <5.0, the rate decreases with increasing concentration of the exchanging ion. At physiological pH, the kinetic inertness of [DTPA-(Me-Trp)(2)] is more inert than GdDTPA(2-), the most commonly used MRI contrast agent (t(1/2) = 127 h). High kinetic stability is an important requirement for the Gd complexes used as contrast enhancement agents in magnetic resonance imaging.
二亚乙基三胺五乙酸（DTPA）-双（酰胺）类似物已被合成并评估为有潜力的生物医学成像剂。在小鼠中进行了成像和生物分布研究，结果表明 DTPA 类似物在大脑中显著积累。通过 pH 电位法（Gd(3+)、Eu(3+)）和分光光度法（Cu(2+)）在 25°C 和恒定离子强度下（由 0.10 M KCl 维持）确定了配体[DTPA-(Me-Trp)(2)]与 Gd(3+)、Eu(3+)和 Cu(2+)形成的配合物的稳定性和质子化常数。通过与 Zn(2+)和 Eu(3+)的交换反应速率，表征了 Gd [DTPA-(Me-Trp)(2)]的动力学惰性。在 Eu(3+)交换中，发现准一级速率常数的[H(+)]依赖性为二级[k(0) = (4.5 ± 1.2) × 10(-6)/s；k(1) = 0.58 ± 0.1 /M/s，k(2) = (6.6 ± 0.2) × 10(4) /M(2)/s，k(3) = (4.8 ± 0.8) × 10(-4) /M/s]。在 Eu(3+)交换中，在 pH <5.0 时，速率随交换离子浓度的增加而降低。在生理 pH 值下，[DTPA-(Me-Trp)(2)]的动力学惰性比最常用的 MRI 造影剂 GdDTPA(2-)更惰性（t(1/2) = 127 h）。高动力学稳定性是作为磁共振成像增强剂的 Gd 配合物的重要要求。
