Human (13)N-ammonia PET studies: the importance of measuring (13)N-ammonia metabolites in blood

Metab Brain Dis. 2010 Mar;25(1):49-56. doi: 10.1007/s11011-010-9181-2. Epub 2010 Mar 9.

Abstract

Dynamic (13)N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood (13)N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of (13)N-content in blood into (13)N-ammonia, (13)N-urea, (13)N-glutamine and (13)N-glutamate. Due to a radioactive half-life for (13)N of 10 min, the procedure is not suitable for blood samples taken beyond 5-7 min after tracer injection. By modifying Rosenspire's method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate (13)N-ammonia injections with a 60-min interval. Blood data from a (13)N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of (13)N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of (13)N-ammonia to (13)N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total (13)N-concentration in blood as input function, whereas assessment of metabolic processes requires (13)N-ammonia measurements.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonia / analysis*
  • Ammonia / blood*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Chemistry / physiology
  • Chromatography, High Pressure Liquid
  • Hepatic Encephalopathy / diagnostic imaging*
  • Hepatic Encephalopathy / metabolism
  • Hepatic Encephalopathy / physiopathology
  • Humans
  • Hyperammonemia / diagnostic imaging*
  • Hyperammonemia / metabolism
  • Hyperammonemia / physiopathology
  • Kinetics
  • Neurochemistry / methods
  • Nitrogen Radioisotopes
  • Positron-Emission Tomography / methods*
  • Predictive Value of Tests
  • Time Factors

Substances

  • Nitrogen Radioisotopes
  • Ammonia