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Purpose <p>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).</p> Procedures <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Pharmacokinetic Modeling of Hepatospecific MRI Contrast Agent Flux in Large Animal Models by Dynamic Contrast-Enhanced MRI

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Matthew T. Latourette,
  • Jeremy M. L. Hix,
  • Jie Huang,
  • Christiane L. Mallett,
  • Kirk A. Muñoz,
  • Erik M. Shapiro

摘要

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.