Gadolinium-ethoxybenzyl-DTPA, a new liver-directed magnetic resonance contrast agent. Absence of acute hepatotoxic, cardiovascular, or immunogenic effects.
OBJECTIVE
Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a recently introduced experimental magnetic resonance (MR) contrast agent for hepatic imaging. Although liver enhancement has been investigated in a number of animal models, tolerance evaluations of Gd-EOB-DTPA injection have been limited.


METHODS
The authors investigated acute hepatotoxicity in an isolated perfused rat liver model, cardiovascular effects in the anesthetized rat, and potential immunogenicity of Gd-EOB-DTPA using detection of specific antibodies.


RESULTS
Using perfused rat liver model, no significant deviation could be observed for functional parameters, liver enzymes, or potassium release, comparing Gd-EOB-DTPA to a control, but there was a significant choleresis (+250% bile flow). Hemodynamic effects of Gd-EOB-DTPA were observed after femoral bolus injection, but only with relatively high dosages (0.3-0.5 mmol/kg, 10-fold the likely clinical dose in humans). Experimental conditions, idealized for antibody induction, failed to cause an IgG immune response to Gd-EOB-DTPA in the intact rat.


CONCLUSIONS
The results further support preliminary conclusions that Gd-EOB-DTPA is a well-tolerated MR contrast agent.
Mühler
A
A
Contrast Media Laboratory, University of California, San Francisco 94143-0628.
Clément
O
O
Saeed
M
M
Lake
J R
JR
Stites
D P
DP
Berthezène
Y
Y
Brasch
R C
RC
D000818:Animals; D001646:Bile / Q000187:drug effects; D003287:Contrast Media / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019786:Gadolinium DTPA; D006439:Hemodynamics / Q000187:drug effects*; D007074:Immunoglobulin G / Q000187:drug effects*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects*; D008107:Liver Diseases / Q000175:diagnosis; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity*; D004369:Pentetic Acid / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D007074:Immunoglobulin G; D009942:Organometallic Compounds; C073590:gadolinium ethoxybenzyl DTPA; D004369:Pentetic Acid; D019786:Gadolinium DTPA