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Kinetics of Formation for Lanthanide (III) Complexes of DTPA-(Me-Trp)2 used as Imaging Agent


Corresponding author: Anil K. Mishra,


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 Gd3+, Eu3+, and Cu2+ have been determined by pH potentiometry (Gd3+, Eu3+) and spectrophotometry (Cu2+) 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 Zn2+ and Eu3+. In the Eu3+ exchange, a second-order [H+] dependence was found for the pseudo-first-order rate constant [k0 = (4.5 ± 1.2) × 10−6/s; k1 = 0.58 ± 0.1 /m/s, k2 = (6.6 ± 0.2) × 104 /m2/s, k3 = (4.8 ± 0.8) × 10−4/m/s]. In the Eu3+ 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 GdDTPA2−, the most commonly used MRI contrast agent (t1/2 = 127 h). High kinetic stability is an important requirement for the Gd complexes used as contrast enhancement agents in magnetic resonance imaging.