RETRACTED: Kinetics of Formation for Lanthanide (III) Complexes of DTPA-(Me-Trp)2 used as Imaging Agent (Retracted Article)

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 degrees 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 [k(0) = (4.5 +/- 1.2) x 10-6/s; k(1) = 0.58 +/- 0.1 /m/s, k(2) = (6.6 +/- 0.2) x 104 /m2/s, k(3) = (4.8 +/- 0.8) x 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 (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.