There was a significant difference in striatal [11C]raclopride binding potential between the balanced drink condition (mean=2.6, SD=0.3) and the tyrosine/phenylalanine depleted drink condition (mean=2.7, SD=0.3) (t=–5.10, df=6, p=0.002); dietary tyrosine/phenylalanine depletion increased [11C]raclopride binding potential in the striatum by a mean of 6% (SD=3%). The statistical parametric mapping analysis (F1) confirmed the findings of the region of interest analysis. The simplified reference tissue model also showed a significant increase in binding potential (t=–3.6, df=6, p=0.01), as did analysis with fixed-volume regions of interest (t=–3.8, df=6, p=0.009). There was a significant increase in plasma prolactin concentration (an indirect measure of reduced dopamine transmission in the hypothalamus) from 4 hours before drink ingestion to 100 minutes after for the depleted drink condition (mean=177 [SD=56] versus 314 [SD=140], respectively) compared with the balanced drink condition (mean=184 [SD=53] and 145 [SD=39]) (F=5.86, df=2, 12, p<0.02). The change in ratio of plasma tyrosine and phenylalanine to large neutral amino acids was significantly greater for the depleted drink condition (tprescan: mean= 0.21 [SD=0.04]; tend: mean=0.0067 [SD=0.0038]) than for the balanced drink condition (tprescan: mean=0.23 [SD=0.03]; tend: mean=0.12 [SD=0.03]) (F=55.37, df=2, 12, p<0.001). The absolute concentration of tyrosine and phenylalanine was also lower relative to baseline in the depleted drink condition (–74%, SD=9) than in the balanced drink condition (266%, SD=147) (F=22.67, df=2, 12, p<0.001). Most importantly, the increase in binding potential following tyrosine and phenylalanine depletion correlated significantly with the percentage fall in the ratio of tyrosine and phenylalanine to large neutral amino acids (r=0.79, df=5, p=0.03), providing validation that the increase of [11C]raclopride binding was related to dopamine precursor availability.
Reference tissue time activity curve, region of interest volume, and radiopharmaceutical parameters (total injected, precursor injected, purity, and specific radioactivity) did not differ between conditions (data not shown).