Gd-DOTA: characterization of a new paramagnetic complex.
The relaxivity, biodistribution, and toxicity of the gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) complex were evaluated. This cyclic complex has much greater in vitro stability (10(28)) than similar noncyclic complexes such as gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) (10(23)) or gadolinium-ethylenediaminetetraacetic acid (Gd-EDTA) (10(17)). The T1 relaxivity of Gd-DOTA (meglumine salt) determined in saline and in liver tissue at 20 MHz was similar to the relaxivity of Gd-DTPA. Tissue proton relaxation enhancement (PRE) correlated closely with chemical measurement of tissue gadolinium concentration. In rats, the biodistribution of Gd-DOTA was similar to Gd-DTPA with a distribution half-life of 3 minutes and an elimination half-life of 18 minutes. The median lethal dose (LD50) in mice of Gd-DOTA was 93% higher than that of Gd-DTPA; the calculated safety factor (ratio of LD50 to effective dose) was 53 for Gd-DOTA and 28 for Gd-DTPA. The data suggest that in vitro stability correlates with in vivo safety.
Bousquet
J C
JC
Department of Radiology, Massachusetts General Hospital, Boston 02114.
Saini
S
S
Stark
D D
DD
Hahn
P F
PF
Nigam
M
M
Wittenberg
J
J
Ferrucci
J T
JT
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005682:Gadolinium / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D008280:Magnetics; D051379:Mice; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D004369:Pentetic Acid; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium; D019786:Gadolinium DTPA