title: Evaluation of two new gadolinium chelates as contrast agents for MRI.
abstract: Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N''-bis(3-hydroxy-6-methyl-2- pyridylmethyl)diethylenetriamine-N,N',N''-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7,13-triaza-4,10,16-trioxacyclooctadecane-N,N', N''-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T1-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.
authors.affiliation: Edward Mallinckrodt Institute of Radiology, Washington University Medical School, St. Louis, MO 63110.
authors.forename: C B
authors.initials: CB
authors.lastname: Wiegers
authors.forename: M J
authors.initials: MJ
authors.lastname: Welch
authors.forename: T L
authors.initials: TL
authors.lastname: Sharp
authors.forename: J J
authors.initials: JJ
authors.lastname: Brown
authors.forename: W H
authors.initials: WH
authors.lastname: Perman
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: R J
authors.initials: RJ
authors.lastname: Motekaitis
authors.forename: A E
authors.initials: AE
authors.lastname: Martell
mesh_terms: D000085:Acetates / Q000493:pharmacokinetics; D000818:Animals; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000085:Acetates; D003287:Contrast Media; D009942:Organometallic Compounds; C078663:gadolinium-N,N''-bis(3-hydroxy-6-methyl-2-pyridylmethyl)diethylenetriamine-N,N',N''-triacetic acid; C078664:gadolinium-1,7,13-triaza-4,10,16-trioxacyclooctadecane-N,N',N''-triacetic acid; D004369:Pentetic Acid; D019786:Gadolinium DTPA