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

Abstract

Dynamic 13N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood 13N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of 13N-content in blood into 13N-ammonia, 13N-urea, 13N-glutamine and 13N-glutamate. Due to a radioactive half-life for 13N 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 13N-ammonia injections with a 60-min interval. Blood data from a 13N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of 13N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of 13N-ammonia to 13N-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 13N-concentration in blood as input function, whereas assessment of metabolic processes requires 13N-ammonia measurements.

Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC

“…For example, 13 N-labeled metabolites (urea, glutamine, glutamate) accumulate in the blood and account for 40%-80% of the total activity as early as 5 minute after injection of 13 N-ammonia. 16 With older 2D PET systems, a single static scan may be adequate for accurate integration of the blood time-activity data, 17 because dead-time losses and random rates are low and change relatively slowly over time. However, with current 3D PET systems, dead-time losses and random rates are much higher and more rapidly changing during the bolus first-pass transit; therefore, dynamic imaging with reconstruction of sequential short time-frames is typically required for accurate sampling and integration of the arterial blood activity.…”

Effect of Glutamine Synthetase Inhibition on Brain and Interorgan Ammonia Metabolism in Bile Duct Ligated Rats

“…We chose to use the stable isotope 15 N-ammonia because of high analytical accuracy and precision of the GC-MS measurement of the relative 15 N-labeling of amino acids in tissue samples which cannot be obtained by administration of tracer doses of for example positron-labeled 13 N-ammonia. 35 The use of non-tracer doses of 15 N-ammonia may also have blurred potential differences in amino-acid metabolism between sham and BDL rats.…”

Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

“…Additional arterial blood samples of 2 mL were collected at 1, 2, 3, 5, 7, 10, 15, 20, 25, and 30 minutes after 13 N-ammonia administration for determination of blood concentrations of 13 N-ammonia, 13 N-urea, and 13 N-glutamine. 17 Analysis of PET Data. Analysis of the 15 O-water PET data was performed using a standard clinical method implemented at our institution; each PET recording was registered to a PET template in the Talairach space.…”