Determination of hepatic galactose elimination capacity using 2-[¹⁸F]fluoro-2-deoxy-d-galactose PET/CT: reproducibility of the method and metabolic heterogeneity in a normal pig liver model

Abstract

Objective. A PET method is developed for non-invasive measurement of regional metabolic liver function using the galactose analog 2-[¹⁸F]fluoro-2-deoxy-d-galactose, FDGal. The aim of the present study was to determine the reproducibility of the method in pigs before translating it to human studies. Material and methods. Five anesthetized pigs were studied twice within an interval of three days. A dynamic PET recording was performed with an injection of 100 MBq FDGal. Non-radioactive galactose was administered throughout the PET recordings to achieve near-saturated elimination kinetics. Arterial blood samples were collected for determination of blood concentrations of FDGal and galactose (c_gal). Net metabolic clearance of FDGal, K_FDGal, was calculated from linear representation of data. The approximate maximal hepatic removal rate, V_max, of galactose (mmol/l tissue/min) was calculated as K_FDGal c_gal. The estimates from Day 1 and Day 2 were compared and the coefficient of variation, COV, of the estimates calculated. Functional heterogeneity in normal pig liver was evaluated as COV of the tissue concentration of radioactivity during quasi steady-state metabolism. Results. There was no significant difference between V_max from Day 1 and Day 2 (p = 0.38), and the reproducibility was good with a COV of 14% for the whole liver. In normal pig liver tissue, mean COV after an injection of FDGal was on average 15.6% with no day-to-day variation (p = 0.7). Conclusions. The novel FDGal PET method for determination of hepatic metabolic function has a good reproducibility and is promising for future human studies of regional liver function.

Key Words::

• Galactose elimination capacity
• hepatobiliary
• liver metabolism
• nuclear hepatology
• physiology

Acknowledgements

The author thanks the highly skilled staff at the PET Center, Aarhus University Hospital, especially veterinarian Aage Kristian Astrup Olsen without whom the project could not have been conducted. The author would also like to thank Susanne Keiding for fruitful discussions on the paper. The study was supported by grants from the NIH (R01 DK074419-01), the Danish Medical Research Council (271-06-0357), the Danish Cancer Society (DP06114), Aarhus University Foundation, the Novo Nordisk Foundation, and the A.P. Møller Foundation for the Advancement of Medical Science.

Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.