Patients with
phenylketonuria (PKU) may suffer from cognitive and neurological deficits which are related to reduced intracerebral concentrations of
catecholamines. The function of
phenylalanine (Phe) as an inhibitor of the uptake of the precursor
amino acid tyrosine (Tyr) through the blood-brain barrier as well as an inhibitor of the expression of
dopamine receptors in the brain is under investigation. Positron emission tomography (PET) is a method for quantitatively determining biochemical and physiological processes in vivo. In the current pilot study, L-[1-11C]-Tyr and 18F-fluoro-ethyl-spiperone (
FESP) have been used. The metabolic pathway of carboxylic labelled Tyr is mainly incorporation into
protein. From the measured tissue and plasma activity as a function of time in combination with a compartimental model the
Protein Synthesis Rate (PSR) for Tyr can be calculated.
FESP is a
ligand which binds irreversibly to the
dopamine D2-receptor and has also a low non specific binding, although affinity to the
serotonin receptor has been described. The ratio of
FESP concentration in striatum and in cerebellum is a measure of the receptor status in vivo. In patients with plasma Phe levels above the maximum therapeutic concentration (> 700 mumol/l) the PSR for Tyr was decreased as compared to controls and patients with plasma Phe concentrations within the therapeutic range, indicating a decreased availability of Tyr for
neurotransmitter synthesis, and hence explaining the reduced cerebral concentration of
catecholamines.