This will be an open label, non-randomised \[11C\]PHNO PET study using healthy male volunteers. Each volunteer will undergo 4 \[11C\]PHNO PET scans to allow for further characterisation of this radioligand and examine the effects of \[11C\]PHNO mass carry-over and displaceable binding in the brain. This study aims to obtain data from 6 evaluable subjects.
A test-retest (TRT) investigation of \[11C\]PHNO in human is required to further characterise \[11C\]PHNO. \[11C\] PHNO possesses very high affinity for the D3 receptor, and therefore most clinical studies are conducted at D3 occupancies \>10%. As \[11C\]PHNO kinetics in the target brain regions are moderately slow, considerable mass carry over may be present on a 2nd PET scan conducted on the same day. In addition there appears to be a significant displaceable binding component in the cerebellum, which, if not accounted for, will lead to a bias in the quantification of specific \[11C\]PHNO binding. The aim of this study is therefore to examine the effects of \[11C\]PHNO mass carry-over and displaceable binding in the cerebellum, on the quantification of \[11C\]PHNO PET data. This will be an open label, non-randomised \[11C\]PHNO PET study using healthy volunteers. Each volunteer will undergo 4 \[11C\]PHNO PET scans: 1st and 2nd scans; TRT on the same day with a minimal gap between \[11C\]PHNO injections to examine the effects of PHNO mass carry over, 3rd scan \>1 week later to determine the "true" TRT variability and a 4th scan will follow a 15mg dose of aripiprazole (a D2/D3 compound which allows the highest clinically acceptable blockade of central D2/D3 receptors) and will examine the amount of displaceable binding in the cerebellum, a proposed reference tissue for \[11C\]PHNO. The scan data will be quantified as regional volumes of distribution (VT).
Study Type
INTERVENTIONAL
Allocation
NA
Masking
NONE
Enrollment
7
examine the effects of \[11C\]PHNO mass carry-over and displaceable binding
A 4th scan will follow a 15mg dose of aripiprazole (a D2/D3 compound which allows the highest clinically acceptable blockade of central D2/D3 receptors)
GSK Investigational Site
London, London, United Kingdom
volume of distribution
Regional volume of distribution (VT) in sub-cortical, brainstem and cerebellar regions of interest at each PET scan.
Time frame: one year
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