European journal of nuclear medicine and molecular imaging · 2026
Continuous infusion [11C]-(+)-PHNO PET for measuring dopamine D2/3 receptor availability and amphetamine effects across the brain: Feasibility and test-retest reliability.
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Dajic Irena, Sauerzopf Ulrich, Weidenauer Ana, Diendorfer Cornelia, Landesmann Katharina, Rausch Ivo, Hahn Andreas, Spurny-Dworak Benjamin, Klöbl Manfred, Reed Murray, Lanzenberger Rupert, Bauer Martin, Zeitlinger Markus, Bartova Lucie, Wolkersdorfer Martin, Nics Lukas, Wadsak Wolfgang, Hacker Marcus, Philippe Cécile, Praschak-Rieder Nicole, Willeit Matthäus
Аннотация
PURPOSE: Dopamine D2/3 receptors are expressed throughout the human brain, but synchronous receptor quantification in subcortical and cortical brain areas remains difficult to achieve with a single radioligand. Here, we assessed the suitability of a bolus plus constant infusion (B/I) paradigm for brain-wide dopamine D2/3 receptor imaging with the agonist radioligand [11C]-(+)-PHNO.
METHODS: Five healthy male volunteers underwent two B/I [11C]-(+)-PHNO positron emission tomography (PET) scans combined with a mid-scan intravenous amphetamine challenge. Non-displaceable binding potentials (BPND) were calculated using the equilibrium ratio method and an algorithmically constrained cerebellum as the reference region.
RESULTS: Reproducible baseline BPND values were obtained for the majority of regions examined, with intraclass correlation coefficients ranging from 0.5 to 0.93, and test-retest variability remaining below 10%. Moreover, amphetamine-induced decreases in receptor binding were observed in both scans in cortical and a number of subcortical regions. In the globus pallidus and ventral striatum, however, equilibrium had not been reached prior to amphetamine injection, suggesting that further optimization of the protocol might be needed to quantify amphetamine effects in D3 receptor-rich regions.
CONCLUSIONS: These results indicate that, within certain limitations, synchronous cortical and subcortical measurements of D2/3 receptors at baseline and under challenge conditions can be achieved using the B/I approach and [11C]-(+)-PHNO PET.
METHODS: Five healthy male volunteers underwent two B/I [11C]-(+)-PHNO positron emission tomography (PET) scans combined with a mid-scan intravenous amphetamine challenge. Non-displaceable binding potentials (BPND) were calculated using the equilibrium ratio method and an algorithmically constrained cerebellum as the reference region.
RESULTS: Reproducible baseline BPND values were obtained for the majority of regions examined, with intraclass correlation coefficients ranging from 0.5 to 0.93, and test-retest variability remaining below 10%. Moreover, amphetamine-induced decreases in receptor binding were observed in both scans in cortical and a number of subcortical regions. In the globus pallidus and ventral striatum, however, equilibrium had not been reached prior to amphetamine injection, suggesting that further optimization of the protocol might be needed to quantify amphetamine effects in D3 receptor-rich regions.
CONCLUSIONS: These results indicate that, within certain limitations, synchronous cortical and subcortical measurements of D2/3 receptors at baseline and under challenge conditions can be achieved using the B/I approach and [11C]-(+)-PHNO PET.