PURPOSE: 6-[(18)F]fluoro-L-3,4-dihydroxyphenyl alanine ([(18)F]FDOPA) positron emission tomography (PET) is a diagnostic tool which can detect malignancies of the pancreas. We aimed to study whether the manipulation of the [(18)F]FDOPA metabolic pathway would change the (18)F-behavior to provide a biochemical foundation for PET imaging of rat pancreas with [(18)F]FDOPA. PROCEDURES: Inhibitors of aromatic amino acid decarboxylase, catechol-O-methyltransferase, monoamine oxidases A and B, or their combinations on [(18)F]FDOPA uptake, metabolism, and the regional distribution in the rat pancreas was evaluated using in vivo PET/computed tomography imaging, chromatographic metabolite analyses, and autoradiography. RESULTS: Enzyme inhibition generally increased the uptake of [(18)F]FDOPA derived (18)F-radioactivity in rat pancreas. Dependent on which enzymatic pathway is blocked (or a combination of pathways), different radiolabeled metabolites in pancreas are responsible for this increase in uptake. CONCLUSIONS: Altering the metabolism of [(18)F]FDOPA by using various enzymatic inhibitors increased the radioactivity uptake and changed the radiometabolic profile in the pancreas allowing better discrimination between pancreas and surrounding tissues of rat. However, these manipulations did not separate islets from the exocrine pancreas. Elucidating the metabolic behavior of [(18)F]FDOPA provides a biochemical foundation of PET imaging of the rat pancreas.
PURPOSE:6-[(18)F]fluoro-L-3,4-dihydroxyphenyl alanine ([(18)F]FDOPA) positron emission tomography (PET) is a diagnostic tool which can detect malignancies of the pancreas. We aimed to study whether the manipulation of the [(18)F]FDOPA metabolic pathway would change the (18)F-behavior to provide a biochemical foundation for PET imaging of rat pancreas with [(18)F]FDOPA. PROCEDURES: Inhibitors of aromatic amino acid decarboxylase, catechol-O-methyltransferase, monoamine oxidases A and B, or their combinations on [(18)F]FDOPA uptake, metabolism, and the regional distribution in the rat pancreas was evaluated using in vivo PET/computed tomography imaging, chromatographic metabolite analyses, and autoradiography. RESULTS: Enzyme inhibition generally increased the uptake of [(18)F]FDOPA derived (18)F-radioactivity in rat pancreas. Dependent on which enzymatic pathway is blocked (or a combination of pathways), different radiolabeled metabolites in pancreas are responsible for this increase in uptake. CONCLUSIONS: Altering the metabolism of [(18)F]FDOPA by using various enzymatic inhibitors increased the radioactivity uptake and changed the radiometabolic profile in the pancreas allowing better discrimination between pancreas and surrounding tissues of rat. However, these manipulations did not separate islets from the exocrine pancreas. Elucidating the metabolic behavior of [(18)F]FDOPA provides a biochemical foundation of PET imaging of the rat pancreas.
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