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Pharmacokinetic Modeling of Hepatospecific MRI Contrast Agent Flux in Large Animal Models by Dynamic
Matthew T Latourette1,2, Jeremy M L Hix1,2, Jie Huang1
1Department of Radiology, Michigan State University, 846 Service Rd, East Lansing, MI, 48824, USA.
Purpose:
Evaluate the feasibility of using dogs and a pig as translational models for assessing hepatic flux of hepatospecific gadolinium-based contrast agents using dynamic contrast-enhanced MRI (DCE-MRI).
Procedures:
DCE-MRI was performed with hepatospecific agents, gadoxetate disodium (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA), and non-hepatospecific agents. Two validated pharmacokinetic models were applied: a single-input reference region model and a dual-input model using arterial and venous blood signals.
Results:
In dogs, hepatic enhancement rose rapidly and plateaued after Gd-EOB-DTPA administration, with minimal decline over an hour. In the pig, both hepatospecific agents showed a rapid rise, blunt peak, and gradual decline. The single-input model revealed significantly higher uptake rates for hepatospecific agents, confirming its sensitivity to hepatocyte uptake. The dual-input model effectively distinguished contrast agent dynamics in dogs and showed promise in the pig.
Conclusions:
In this feasibility study, the enhancement dynamics observed and pharmacokinetic estimates computed in both dogs and a pig fell broadly within ranges reported in human studies, supporting their potential utility as translational large-animal models. Definitive comparison of species similarity to humans will require direct paired evaluation under matched conditions.
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