Enzyme inhibition of dopamine metabolism alters 6-[(18)F]FDOPA uptake in orthotopic pancreatic adenocarcinoma

BACKGROUND: An unknown location hampers removal of pancreatic tumours. We studied the effects of enzyme inhibitors on the uptake of 6-[(18)F]fluoro-l-3,4-dihydroxyphenylalanine ([(18)F]FDOPA) in the pancreas, aiming at improved imaging of pancreatic adenocarcinoma. METHODS: Mice bearing orthotopic BxPC3 pancreatic adenocarcinoma were injected with 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) and scanned with positron emission tomography/computed tomography (PET/CT). For [(18)F]FDOPA studies, tumour-bearing mice and sham-operated controls were pretreated with enzyme inhibitors of aromatic amino acid decarboxylase (AADC), catechol-O-methyl transferase (COMT), monoamine oxidase A (MAO-A) or a combination of COMT and MAO-A. Mice were injected with [(18)F]FDOPA and scanned with PET/CT. The absolute [(18)F]FDOPA uptake was determined from selected tissues using a gamma counter. The intratumoural biodistribution of [(18)F]FDOPA was recorded by autoradiography. The main [(18)F]FDOPA metabolites present in the pancreata were determined with radio-high-performance liquid chromatography. RESULTS: [(18)F]FDG uptake was high in pancreatic tumours, while [(18)F]FDOPA uptake was highest in the healthy pancreas and significantly lower in tumours. [(18)F]FDOPA uptake in the pancreas was lowest with vehicle pretreatment and highest with pretreatment with the inhibitor of AADC. When mice received COMT + MAO-A inhibitors, the uptake was high in the healthy pancreas but low in the tumour-bearing pancreas. CONCLUSIONS: Combined use of [(18)F]FDG and [(18)F]FDOPA is suitable for imaging pancreatic tumours. Unequal pancreatic uptake after the employed enzyme inhibitors is due to the blockade of metabolism and therefore increased availability of [(18)F]FDOPA metabolites, in which uptake differs from that of [(18)F]FDOPA. Pretreatment with COMT + MAO-A inhibitors improved the differentiation of pancreas from the surrounding tissue and healthy pancreas from tumour. Similar advantage was not achieved using AADC enzyme inhibitor, carbidopa.