Gadolinium complexes of [(myristoyloxy)propyl]diethylenetriaminetetraacetate: new lipophilic, fatty acyl conjugated NMR contrast agents.
New lipophilic contrast agents, 1-[3'-(myristoyloxy)propyl]diethylenetriamine-1,4,7,7-tetraacetic acid (1MP-DTTA), 4-[3'-(myristoyloxy)propyl]diethylenetriamine-1,1,7,7-tetraacetic acid (4MP-DTTA), and 4-[3'-(myristoyloxy)propyl]-2,6-dioxodiethylenetriamine-1,1, 7, 7-tetraacetic acid (4MPD-DTTA), were prepared from either diethylenetriamine or 3-amino-1-propanol (overall yield 16-23%). Liposome-incorporated Gd complexes of ligands 1MP-DTTA, 4MP-DTTA, and 4MPD-DTTA were prepared by mixing GdCl3 and the prepared vesicles consisting of ligand, egg lecithin, and cholesterol (molar ratio 1.1:5.1) followed by further sonication, and their in vitro relaxivities were determined. The relaxivities of these agents were higher than those of the Gd3+ aquoion, Gd(EDTA), or Gd(DTPA) at both 0.23 and 0.47 T. Gd(4MPD-DTTA) displayed the highest relaxivities (24.0 +/- 0.4 and 34.7 +/- 0.4, at 0.23 and 0.47 T, respectively) among these new Gd complexes. The relaxivities of these three agents increased from the lower to the higher magnetic field, indicating a positive field dependence. Stability constants (log K) of Gd(1MP-DTTA), Gd(4MP-DTTA), and Gd(4MPD-DTTA) were found to be 18.2 +/- 0.2, 18.4 +/- 0.2, and 15.7 +/- 0.8, respectively. A lower limit of 0.3 mmol/kg was found for LD50 for these three agents.
Kim
S K
SK
Department of Medicine, University of Alabama, Birmingham 35294.
Pohost
G M
GM
Elgavish
G A
GA
D001665:Binding Sites; D003287:Contrast Media; D005682:Gadolinium / Q000737:chemistry*; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
C075466:1-(3'-(myristoyloxy)propyl)diethylenetriamine-1,4,7,7-tetraacetic acid gadolinium complex; C075465:4-(3'-(myristoyloxy)propyl)-2,6-dioxodiethylenetriamine-1,1,7,7-tetraacetic acid gadolinium complex; C075464:4-(3'-(myristoyloxy)propyl)diethylenetriamine-1,1,7,7-tetraacetic acid gadolinium complex; D003287:Contrast Media; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA