Simultaneous measurement of [¹⁸F]FDOPA metabolism and cerebral blood flow in newborn piglets

Abstract

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.

Effect of Moderate Hypercapnic Hypoxia on Cerebral Dopaminergic Activity and Brain O2 Uptake in Intrauterine Growth–Restricted Newborn Piglets

“…Nevertheless, the estimation of AADC activity by compartmental analysis of transport and metabolism of FDOPA in newborn piglets was confirmed previously (14,25). Furthermore, the amount of combined respiratory and metabolic acidosis as well as the estimated cardiovascular effects owing to prolonged H/H were widely similar in newborn normal-weight and IUGR piglets.…”

“…18 F]F 2 (24) simplifying the procedure [see (25)]. The piglets were studied lying prone in the scanner (CTI/Siemens ECAT EXACT HRϩ; dynamic scans: 35 frames between 30 and 600 s each, total length 120 min).…”

“…Plasma activity (100 L) was measured in a well counter (COBRA II) cross-calibrated with the tomograph. In addition, nine blood samples (at 2,4,8,12,16,25,50,90, and 120 min) were withdrawn for HPLC analysis to correct the plasma input function for the presence of FDOPA metabolites (26). PET imaging was performed with an ECAT EXACT HRϩ (CTI/Siemens) scanner at a spatial resolution (transaxial) of 4 -5 mm (27).…”

L-Type Amino Acid Transporters LAT1 and LAT4 in Cancer: Uptake of 3-O-Methyl-6- 18F-Fluoro-L-Dopa in Human Adenocarcinoma and Squamous Cell Carcinoma In Vitro and In Vivo

“…In the past, 18 F-OMFD was considered mainly as a metabolite of 6-18 F-fluoro-L-3,4-dihydroxyphenylalanine that is able to pass the blood-brain barrier, thereby contributing to 18 F uptake in the striatum. Therefore, it has to be considered for the formulation of a quantitative 6-18 F-fluoro-L-3,4-dihydroxyphenylalanine kinetic model (25). 18 F-OMFD, a methoxy derivative of the amino acid tracer 2-18 F-fluoro-L-tyrosine (26), is supposed to be a promising PET tracer for imaging the functional expression of amino acid transport systems in tumors.…”

Intrauterine Growth Restriction Induces Up-Regulation of Cerebral Aromatic Amino Acid Decarboxylase Activity in Newborn Piglets: [18F]Fluorodopa Positron Emission Tomographic Study

“…Flows are expressed in milliliters per minute per 100 g tissue by normalizing for tissue weight. Blood O 2 content (cO 2 ) was calculated using the equation (17), simplifying the procedure (18). The piglets were studied lying prone in the scanner (CTI/Siemens ECAT EXACT HRϩ; dynamic scans, 35 frames between 30 and 600 s each; total length, 120 min).…”