[¹²³I]TPCNE - A novel SPET tracer for the sigma-1 receptor: First human studies and in vivo haloperidol challenge

James M. Stone*, Erik Årstad, Kjell Erlandsson, Rikki N. Waterhouse, Peter J. Ell, Lyn S. Pilowsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


[123I]TPCNE (1(trans-[123I]iodopropen-2-yl)-4-[(4- cyanophenoxy)methyl] piperidine; Ki = 0.67 nM; log P = 3.36) is a novel sigma-1 receptor SPET ligand. In this study, we developed an optimized labeling method for [123I]TPCNE and investigated the kinetics, binding characteristics, and whole-body distribution of this tracer for the first time in humans. We also performed a challenge with the sigma-1 receptor antagonist haloperidol against [123I]TPCNE. Seven healthy volunteers were recruited. Dynamic brain SPET scans were performed following i.v. administration of 185 MBq [123I]TPCNE in all seven subjects. Three of the subjects were given oral haloperidol (2.5 mg) ∼1 h before the scan. The dynamic data were analyzed with both reversible and irreversible compartmental models. [123I]TPCNE showed high uptake in brain and liver. All non-haloperidol-treated subjects showed a high whole-brain uptake (average: 8.7% of injected activity). No significant clearance of the tracer was seen up to 30 h post injection. In the haloperidol-treated subjects, the time-activity curves clearly demonstrated clearance of the tracer from the brain. Regional radioactivity concentrations were reduced by haloperidol from 42% in the cerebellum to 73% in the thalamus. [123I]TPCNE demonstrated high brain uptake, with highest binding found in the posterior cingulate. A region in which binding was unaffected by haloperidol pretreatment could not be identified, and the time-activity data were best described by an irreversible model.

Original languageEnglish
Pages (from-to)109-117
Number of pages9
Issue number2
Publication statusPublished - 19 May 2006


  • Antipsychotic drugs
  • Brain
  • Schizophrenia
  • Sigma-1 receptors
  • SPET


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