Background
The sigma-1 receptor is of increasing relevance to neuropsychiatric function and illness (Leonard 2004). [123I]TPCNE (1(trans-[123I]iodopropen-2-yl)-4-[(4-cyanophenoxy)methyl]piperidine; Ki = 0.67 nM; log P = 3.36) is a novel SPET ligand for the sigma-1 receptor which has demonstrated high selectivity and potency for the receptor in pre-clinical studies (Waterhouse et al 1997). Here we report kinetics and characteristics of this tracer in four healthy volunteers, including one individual scanned at time points up to 30 hours after injection.
Method
Four healthy volunteers were recruited (1 female, 3 male, mean age=32). All subjects received a bolus dose of approximately 185 MBq [123I]TPCNE. Dynamic data acquisition with a brain dedicated Picker Prism 3000XP and arterial sampling began simultaneously. Scanning continued at time points up to 3.5 hours in three subjects. In one subject scanning continued at time points up to 5.5 hours on the first day and then continued on the following day up to 30 hours after injection. Data were metabolite-corrected and analysed by compartmental modelling with both reversible and irreversible models.
Results
Blood and plasma curves showed a rapid clearance after peaking between 45 and 60 s p.i., with <1% of the peak value left in plasma at 30 min p.i. The parent fraction was high throughout the scan, going from ∼97% at 10 min p.i. to ∼78% at 60 min p.i. Brain uptake was rapid with a widespread distribution, reaching a maximum between 30 and 90 min p.i., with no significant clearance during the time of the scan. The maximum total brain uptake was ∼8.7% of injected activity. The rank order of tracer uptake in different brain regions was posterior cingulate > cerebellum > thalamus > striatum > cortex > white matter. The two-day scan (n-1) showed that there was practically no clearance of tracer up to 30 hours after injection.
Conclusions
[123I]TPCNE is a promising SPET ligand for the sigma-1 receptor that shows exceptionally high, irreversible brain uptake with highest binding in posterior cingulate.