title: Manipulation of [11C]-5-hydroxytryptophan and 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells.
abstract: [(11)C]-5-Hydroxytryptophan ([(11)C]HTP) and 6-[(18)F]fluoro-3,4-dihydroxy-l-phenylalanine ([(18)F]FDOPA) are used to image neuroendocrine tumors with positron emission tomography. The precise mechanism by which these tracers accumulate in tumor cells is unknown. We aimed to study tracer uptake via large amino acid transporters, peripheral decarboxylation (inhibited by carbidopa), and intracellular breakdown by monoamine oxidase (MAO). [(11)C]HTP and [(18)F]FDOPA tracer accumulation was assessed in a human neuroendocrine tumor cell line, BON. The carbidopa experiments were done in a tumor-bearing mouse model. Intracellular [(11)C]HTP accumulation was 2-fold higher than that of [(18)F]FDOPA. Cellular transport of both tracers was inhibited by amino-2-norbornanecarboxylic acid. The MAO inhibitors clorgyline and pargyline increased tracer accumulation in vitro. Carbidopa did not influence tracer accumulation in vitro but improved tumor imaging in vivo. Despite lower accumulation in vitro, visualization of [(18)F]FDOPA is superior to [(11)C]HTP in the neuroendocrine pancreatic tumor xenograft model. This could be a consequence of the serotonin saturation of BON cells in the in vivo model.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Neels
authors.forename: Klaas P
authors.initials: KP
authors.lastname: Koopmans
authors.forename: Pieter L
authors.initials: PL
authors.lastname: Jager
authors.forename: Laya
authors.initials: L
authors.lastname: Vercauteren
authors.forename: Aren
authors.initials: A
authors.lastname: van Waarde
authors.forename: Janine
authors.initials: J
authors.lastname: Doorduin
authors.forename: Hetty
authors.initials: H
authors.lastname: Timmer-Bosscha
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Brouwers
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga