Manipulation of [C-11]-5-hydroxytryptophan and 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells

Oliver C. Neels, Klaas P. Koopmans, Pieter L. Jager, Laya Vercauteren, Aren van Waarde, Janine Doorduin, Hetty Timmer-Bosscha, Adrienne H. Brouwers, Elisabeth G. E. de Vries, Rudi A. J. O. Dierckx, Ido P. Kema, Philip H. Elsinga*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

50 Citations (Scopus)

Abstract

[C-11]-5-Hydroxytryptophan ([C-11]HTP) and 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine [F-18]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). [C-11] HTP and F-18]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 [C-11]HTP accumulation was 2-fold higher than that of [F-18]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 [F-18]FDOPA is superior to [C-11]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.

Original languageEnglish
Pages (from-to)7183-7190
Number of pages8
JournalCancer Research
Volume68
Issue number17
DOIs
Publication statusPublished - 1-Sep-2008

Keywords

  • POSITRON-EMISSION-TOMOGRAPHY
  • SOMATOSTATIN RECEPTOR SCINTIGRAPHY
  • VESICULAR MONOAMINE TRANSPORTERS
  • CARCINOID-TUMORS
  • IN-VITRO
  • ENDOCRINE TUMORS
  • TRANSMITTER UPTAKE
  • OXIDASE ACTIVITY
  • HUMAN BRAIN
  • PET

Cite this