In vivo kinetics of [18F](N-methyl)benperidol: A novel PET tracer for assessment of dopaminergic D2-like receptor binding

Stephen M. Moerlein, Joel S. Perlmutter, Joanne Markham, Michael J. Welch

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

A novel D2-like receptor-binding radioligand, [18F](N- methyl)benperidol ([18F]NMB), was evaluated via positron emission tomographic (PET) imaging studies of ba boons. [18F]NMB rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and striatum-to- cerebellum ratios as high as 35 were achieved after 3 hours. Pretreatment of an animal with unlabeled receptor-specific antagonists be fore injection of [18F]NMB confirmed that the radioligand bound specifically to central D2- like receptors in vivo, and not to S2- or D1-like receptors. Unlabeled eticlopride displaced striatal [18F]NMB in vivo, showing that D2-like binding is reversible. Receptor-binding by the radioligand was resistant to competitive displacement by synaptic dopamine, as illustrated by the lack of effect of intravenous d-amphetamine on the in vivo localization of [18F]NMB. Studies involving sequential intravenous administration of [18F]NMB, d-amphetamine, and eticlopride show that the radioligand does not undergo agonist mediated internalization with subsequent trapping. The feasibility of applying a three-compartment non-steady state model for quantification of [18F]NMB receptor binding was demonstrated. These in vivo characteristics give [18F]NMB distinct advantages over the PET radiopharmaceuticals currently used for clinical investigation of D2-like receptor binding.

Original languageEnglish
Pages (from-to)833-845
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume17
Issue number8
DOIs
StatePublished - Aug 1997

Keywords

  • Benperidol
  • Dopaminergic D2 receptors
  • Imaging
  • Neuroreceptors
  • Positron emission tomography
  • [F](N- methyl)benperidol

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