Simultaneous measurement of [18F]FDOPA metabolism and cerebral blood flow in newborn piglets.
Available information on the dopamine (DA) metabolism of the immature brain is rare. In order to establish a useful animal model we have performed PET experiments in anesthetized neonatal pigs using 6-[18F]-fluoro-L-DOPA (FDOPA) as tracer. In this study, we have simultaneously determined the cerebral blood flow and the rate constant of FDOPA conversion by the aromatic amino acid decarboxylase, the ultimate enzyme in the synthesis of dopamine. The estimated values of FDOPA decarboxylation in the basal ganglia were similar to values calculated in adult animals and humans. However, in contrast to those studies a significant decarboxylation was also found in the frontal cortex and the cerebellum. HPLC analysis of brain samples also revealed extensive and rapid metabolism of FDOPA in the five investigated brain regions. At 8 min after tracer injection about 80% of FDOPA was already converted to FDA and its metabolites. Surprisingly, a rather high fraction (16-21%) of [18F]-fluoro-3-methoxytyramine was found which may indicate a low storage capacity of vesicular DA at this perinatal stage. It is suggested that the findings are related to the ontogenetic development of the dopaminergic system. The knowledge of the regulation of the DA metabolism in the immature brain may have implications for the understanding of neurodevelopmental effects of perinatal oxygen deprivation.
Brust
P
P
Institut für Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, Dresden, Germany. Brust@FZ-Rossendorf.de
Bauer
R
R
Walter
B
B
Bergmann
R
R
Füchtner
F
F
Vorwieger
G
G
Steinbach
J
J
Johannsen
B
B
Zwiener
U
U
D000818:Animals; D000831:Animals, Newborn; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D008863:Microspheres; D013552:Swine; D013997:Time Factors; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine