title: Kinetics of formation for lanthanide (III) complexes of DTPA-(Me-Trp)2 used as imaging agent.
abstract: 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.
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi-110054, India.
authors.forename: Anjani K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Deepa
authors.initials: D
authors.lastname: Sinha
authors.forename: Anupama
authors.initials: A
authors.lastname: Datta
authors.forename: Dipti
authors.initials: D
authors.lastname: Kakkar
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007553:Isotope Labeling; D007700:Kinetics; D028581:Lanthanoid Series Elements / Q000737:chemistry / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D011199:Potentiometry; D011817:Rabbits; D011868:Radioisotopes; D011877:Radionuclide Imaging; D013667:Technetium / Q000378:metabolism; D014018:Tissue Distribution; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D028581:Lanthanoid Series Elements; D011868:Radioisotopes; D013667:Technetium; D003300:Copper; D004369:Pentetic Acid; D014364:Tryptophan; D015032:Zinc