Abstract
BackgroundAn unknown location hampers removal of pancreatic tumours. We studied the effects of enzyme inhibitors on the uptake of 6-[18F]fluoro-l-3,4-dihydroxyphenylalanine ([18F]FDOPA) in the pancreas, aiming at improved imaging of pancreatic adenocarcinoma.MethodsMice bearing orthotopic BxPC3 pancreatic adenocarcinoma were injected with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and scanned with positron emission tomography/computed tomography (PET/CT). For [18F]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 [18F]FDOPA and scanned with PET/CT. The absolute [18F]FDOPA uptake was determined from selected tissues using a gamma counter. The intratumoural biodistribution of [18F]FDOPA was recorded by autoradiography. The main [18F]FDOPA metabolites present in the pancreata were determined with radio-high-performance liquid chromatography.Results[18F]FDG uptake was high in pancreatic tumours, while [18F]FDOPA uptake was highest in the healthy pancreas and significantly lower in tumours. [18F]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.ConclusionsCombined use of [18F]FDG and [18F]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 [18F]FDOPA metabolites, in which uptake differs from that of [18F]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.
Highlights
An unknown location hampers removal of pancreatic tumours
The aim of this study was to improve the detection of pancreatic adenocarcinoma using positron emission tomography (PET)
Carbidopa pretreatment increased the uptake in the pancreata in both sham-operated and tumour-bearing mice compared with vehicle treatment, but the difference between the sham-operated and tumour-bearing mice was not high enough to separate the healthy pancreas from the tumourbearing pancreas (Figure 2)
Summary
We studied the effects of enzyme inhibitors on the uptake of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) in the pancreas, aiming at improved imaging of pancreatic adenocarcinoma. [18F]FDG is taken up into cells by glucose transporters, where it subsequently undergoes phosphorylation by hexokinase-1 into [18F]FDG-6-phosphate. The most frequently used positron emission tomography (PET) tracer for tumour imaging is the glucose analogue, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). This tracer is efficiently taken up by a variety of tumour cells and reflects increased glucose metabolism [2,3]. Chronic pancreatitis is recognised as the most common reason for false-positive [18F]FDG-PET tumour findings in the pancreas [2,6]
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