[11C]LBT-999: a suitable radioligand for investigation of extra-striatal dopamine transporter with PET

Synapse. 2007 Jan;61(1):17-23. doi: 10.1002/syn.20337.


A new tropane derivative, (E)-N-(4-fluorobut-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl)nortropane (LBT-999), was evaluated in baboons as a carbon-11 radioligand for studies of the dopamine transporter (DAT) using positron emission tomography (PET). Brain uptake was high in the striatum (17 and 13% ID/100 mL tissue in the putamen and the caudate, respectively), moderate in the midbrain and thalamus (5 and 3% ID/100 mL tissue, respectively), and low in the cortex and cerebellum (2% ID/100 mL tissue) at 30 min post injection. The striatum-to-cerebellum ratio was high (30 at 110 min post injection). Specific binding was completely blocked following pretreatment with the DAT antagonists GBR12909 (5 mg/kg i.v.) or PE2I (1 mg/kg i.v.). The [(11)C]LBT-999 uptake was decreased by these antagonists in the putamen (-79 and -92%, respectively), caudate (-80 and -91%, respectively), midbrain (-73 and -78%, respectively), and thalamus (-34 and -46%, respectively). The serotonin transporter (SERT) antagonist citalopram (5 mg/kg i.v.) or the norepinephrine transporter antagonist maprotiline (5 mg/kg i.v.) had no effect on LBT specific binding. Pharmacological challenge with PE2I (1 mg/kg i.v.) induced a rapid and almost complete decrease of the specific binding in the putamen (-97%), caudate (-96%), midbrain (-96%), and thalamus (-81%), confirming the reversibility of [(11)C]LBT-999 binding. The high brain uptake of [(11)C]LBT-999 together with its low nonspecific binding (reflected by the very high brain structure-to-cerebellum ratio) indicate that this radiotracer is an excellent candidate for in vivo quantification of the DAT, especially in extrastriatal structures, such as the midbrain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Radioisotopes
  • Caudate Nucleus / metabolism
  • Cerebral Cortex / metabolism
  • Cocaine / analogs & derivatives
  • Corpus Striatum / metabolism
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Esters* / metabolism
  • Male
  • Mesencephalon / metabolism
  • Nortropanes* / metabolism
  • Papio anubis
  • Positron-Emission Tomography / methods*
  • Putamen / metabolism
  • Thalamus / metabolism


  • 8-((E)-4-fluoro-but-2-enyl)-3beta-p-tolyl-8-aza-bicyclo(3.2.1)octane-2beta-carboxylic acid methyl ester
  • Carbon Radioisotopes
  • Dopamine Plasma Membrane Transport Proteins
  • Esters
  • N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane
  • Nortropanes
  • Cocaine