Imaging nicotinic acetylcholine receptors with fluorine-18-FPH, an epibatidine analog

Victor L. Villemagne, Andrew Horti, Ursula Scheffel, Hayden T. Ravert, Paige Finley, David J. Clough, Edythe D. London, Henry N. Wagner, Robert F. Dannals

Research output: Contribution to journalArticle

Abstract

Nicotinic acetylcholine receptors (nAChRs) have been implicated in a variety of central processes, such as learning and memory and analgesia. These receptors also mediate the reinforcing properties of nicotine in tobacco products and are increased in postmortem samples of brains of smokers. On the other hand, brains of individuals who have died from dementia of the Alzheimer type show abnormally low densities of nAChRs. In this study, the distribution and kinetics of [(±)-exo-2-(2-[18F] fluoro-5-pyridyl)-7- azabicyclo[2.2.1]heptane (18F-FPH), a high-affinity nAChR agonist, was evaluated in a baboon using PET. Methods: After intravenous injection of 5 mCi [185 MBq] 18F-FPH into a 25-kg anesthetized baboon, sequential quantitative tomographic data were acquired over a period of 150 min. Regions of interest were placed and time-activity curves were generated. Brain kinetics of the radiotracer were calculated, and the in vivo regional binding in the baboon brain wee compared with the known in vitro regional distribution of nAChRs in the rat and human brain. Results: Brain activity reached a plateau within 60 min after injection of the tracer, and the binding was reversible. Elimination of 18F-FPH was relatively rapid from the cerebellum (clearance t( 1/4 ) = 3 hr), intermediate from the hypothalamus/midbrain (t( 1/4 ) = 7 hr) and slow from the thalamus (t( 1/4 ) = 16 hr). Radioactivity due to 18F-FPH at 130 min postinjection was highest in the thalamus and hypothalamus/midbrain, intermediate in the neocortex and hippocampus and lowest in the cerebellum. Subcutaneous injection of 1 mg/kg cytisine 45 min after injection of the radiotracer reduced brain activity at 130 min by 67%, 64%, 56% and 52% of control values in the thalamus, hypothalamus/midbrain, hippocampus and cerebellum, respectively. The regional binding of 18F-FPH at 130 min was highly correlated with the known densities of nAChR measured in vitro in human (r = 0.81) and rat brain (r = 0.90). Conclusion: These results demonstrate the feasibility of imaging nAChRs in vivo. Fluorine-18-FPH appears to be a suitable tracer to study nAChRs in the human brain.

Original languageEnglish (US)
Pages (from-to)1737-1741
Number of pages5
JournalJournal of Nuclear Medicine
Volume38
Issue number11
StatePublished - Nov 1 1997

Keywords

  • Brain
  • Epibatidine
  • Nicotinic receptors
  • Nonhuman primate
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Villemagne, V. L., Horti, A., Scheffel, U., Ravert, H. T., Finley, P., Clough, D. J., London, E. D., Wagner, H. N., & Dannals, R. F. (1997). Imaging nicotinic acetylcholine receptors with fluorine-18-FPH, an epibatidine analog. Journal of Nuclear Medicine, 38(11), 1737-1741.