NMR imaging study of the pharmacodynamics of polylysine-gadolinium-DTPA in the rabbit and the rat.
The pharmacodynamics of polylysine-(Gd-DTPA) (Schering, Berlin, Germany), a new blood pooling contrast agent for MRI, were studied in the rabbit and the rat. Polylysine-(Gd-DTPA) is a compound with high LD50. Due to its high molecular weight (50.000) and physico-chemical properties, it remains in the vascular system; during the first hour, the plasma level is three times higher than for Gd-DTPA. MRI was performed at 1.5 T using a SE sequence with TR/TE = 300/15 or 20 msec. Signal intensities of muscle, liver and kidney were measured before and after intravenous injection of the contrast agent (0.1 mmol/kg) during 8 hours in the rat (n = 3) and up to 2 wk in the rabbit (n = 3). A dose response study in three additional rabbits confirmed that the 0.1 mmol/kg dose was optimal. The pharmacodynamics results show that the effects of polylysine-(Gd-DTPA) are similar in both the rabbit and the rat. The liver signal is enhanced by about 60% immediately after injection in both species. This enhanced signal decays to half its maximal value in about one hour, which makes the contrast agent useful for clinical applications at a dose of 0.1 mmol/kg. In the kidney medulla and cortex the signals are enhanced by much larger factors (about 3 to 4); it takes at least one day for the kidney to clear the contrast agent in both species.
Van Hecke
P
P
Department of Radiology, University Hospitals K.U. Leuven, Belgium.
Marchal
G
G
Bosmans
H
H
Johannik
K
K
Jiang
Y
Y
Vogler
H
H
Van Ongeval
C
C
Baert
A L
AL
Speck
U
U
D000818:Animals; D003287:Contrast Media; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D019786:Gadolinium DTPA; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009132:Muscles / Q000033:anatomy & histology / Q000378:metabolism; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000493:pharmacokinetics*; D011107:Polylysine / Q000493:pharmacokinetics* / Q000031:analogs & derivatives; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D003287:Contrast Media; D009942:Organometallic Compounds; C068674:polylysine-(Gd-DTPA); D011107:Polylysine; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA