Amphetamine challenge with [¹⁸F] fallypride: Striatal and extrastriatal measurements in healthy human volunteers

Abstract

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Objectives: The amphetamine challenge (AMPH) has been successfully used to probe dopamine transmission at D2/D3 receptors in striatum using PET and SPECT. The more recently developed D2/D3 antagonist radioligand [¹⁸F] fallypride enables simultaneous quantification of D2/D3 receptors in the striatum and extrastriatal lower receptor density regions. The aim of this study was to investigate the effect of AMPH-induced DA release in both striatal and extrastrial areas in healthy subjects.

Methods: 15 healthy volunteers were scanned at baseline and 30 min following 0.3 mg/kg i.v AMPH on separate days. Scan durations were 240 min, collected in 3 sessions of 50, 60 and 40 min with breaks. Regions of interest were drawn on MRIs and transferred to coregistered PET images. Data were analyzed by 2 tissue compartment modeling (2TC) with arterial input function and SRTM, with cerebellum as reference region. % change of BP_ND following AMPH was computed.

Results: Mean % decreases ± SD and p values for 2TC following AMPH were: posterior putamen(12±17, 0.01) associative striatum (7±16, 0.11) ventral striatum (13±16, 0.01) hippocampus (15±22, 0.01) amygdala (10±16, 0.02) and midbrain (10±15, 0.01). Signal was too low in cortical regions for reliable results. SRTM values were slightly lower but highly correlated with 2TC.

Conclusions: Mean decreases in striatal subregions were similar to literature values for i.v. AMPH. Decreases in moderate binding limbic regions were of comparable magnitude to striatum. No reliable effect of amphetamine was detected in cortical regions The study supports the use of [¹⁸F] fallypride to quantify AMPH challenge in striatum and moderate binding extrastriatal limbic regions simultaneously.

Research Support: NIMH MH0661710-03