Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab

University of Toronto, Toronto, Ontario, Canada
Journal of Cerebral Blood Flow & Metabolism (Impact Factor: 5.41). 10/2007; 27(9):1533-9. DOI: 10.1038/sj.jcbfm.9600493
Source: PubMed


An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.

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Available from: James E Holden, Mar 10, 2014
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    • "Dopamine (DA) D 2 /D 3 receptor availability was indexed with binding potential relative to nondisplaceable binding (BP ND ), which is operationally defined as f ND *B avail /K D (Innis et al., 2007). The cerebellum (vermis excluded) was used as the reference region (tissue that contains few to no D 2 /D 3 receptors ). "
    Dataset: syn21736

    Full-text · Dataset · Jan 2016
    • "Two commonly used estimates of specific binding were considered: BP P =V T ÀV ND and BP ND =V T /V ND À 1, where V ND is the distribution volume of the non-displaceable tissue compartment (approximated by V T in the reference region). BP P represents specific binding relative to arterial plasma, and BP ND represents specific binding relative to the reference region (Innis et al., 2007). "
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    ABSTRACT: The serotonin 5-HT1A receptor is a putative drug development target in disorders with cognitive and in particular memory deficits. However, previous human positron emission tomography (PET) studies on 5-HT1A receptor binding and memory functions have yielded discrepant results. We explored the association between verbal memory and 5-HT1A receptor binding in 24 healthy subjects (14 male, 10 female, aged 18–41 years). The cognitive tests included the Wechsler Memory Scale-Revised (WMS-R), Wechsler Adult Intelligence Scale-Revised (WAIS-R) and Wisconsin Card Sorting Test (WCST). 5-HT1A receptor binding was measured with PET and the radioligand [carbonyl-11C]WAY-100635, which was quantified with the gold standard method based on kinetic modeling using arterial blood samples. We found that global 5-HT1A receptor binding was positively correlated with measures of verbal memory, such that subjects who had higher receptor binding tended to have better verbal memory than subjects who had lower receptor binding. Regional analyses suggested significant correlations in multiple neocortical brain regions and the raphe nuclei. We did not find significant correlations between 5-HT1A receptor binding and executive functions as measured with WCST. We conclude that neocortical as well as raphe 5-HT1A receptors are involved in verbal memory function in man.
    No preview · Article · Dec 2015 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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    • ") (Figure S1) and simplified reference tissue model (SRTM) (Gunn et al., 1997; Innis et al., 2007; Lammertsma and Hume, 1996) (Figure S2). Using the LoganREF model, the volume of distribution ratio (DVR) was estimated in each ROI using a MATLAB (Mathworks Inc., Natick, MA) implementation of these tracer kinetic methods as previously published (Logan et al., 1990). "
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    ABSTRACT: Phosphodiesterase 10A (PDE10A) plays a key role in the regulation of brain striatal signaling. A PET tracer for PDE10A may serve as a tool to evaluate PDE10A expression in vivo in central nervous system disorders with striatal pathology. Here, we further characterized the binding properties of a previously reported radioligand we developed for PDE10A, [(11)C]TZ1964B, in rodents and nonhuman primates (NHPs). The tritiated counterpart [(3)H]TZ1964B was used for in vitro binding characterizations in rat striatum homogenates and in vitro autoradiographic studies in rat brain slices. The carbon-11 labeled [(11)C]TZ1964B was utilized in the ex vivo autoradiography studies for the brain of rats and microPET imaging studies for the brain of NHPs. MicroPET scans of [(11)C]TZ1964B in NHPs were conducted at baseline, as well as with using a selective PDE10A inhibitor MP-10 for either pretreatment or displacement. The in vivo regional target occupancy (Occ) was obtained by pretreating with different doses of MP-10 (0.05 - 2.00 mg/kg). Both in vitro binding assays and in vitro autoradiographic studies revealed a nanomolar binding affinity of [(3)H]TZ1964B to the rat striatum. The striatal binding of [(3)H]TZ1964B and [(11)C]TZ1964B was either displaced or blocked by MP-10 in rats and NHPs. Autoradiography and microPET imaging confirmed that the specific binding of the radioligand was found in the striatum but not in the cerebellum. Blocking studies also confirmed the suitability of the cerebellum as an appropriate reference region. The binding potentials (BPND) of [(11)C]TZ1964B in the NHP striatum that were calculated using either the Logan reference model (LoganREF, 3.96 ± 0.17) or the simplified reference tissue model (SRTM, 4.64 ± 0.47), with the cerebellum as the reference region, was high and had good reproducibility. The occupancy studies indicated a MP-10 dose of 0.31 ± 0.09 mg/kg (LoganREF) / 0.45 ± 0.17 mg/kg (SRTM) occupies 50% striatal PDE10A binding sites. Studies in rats and NHPs demonstrated radiolabelled TZ1964B has a high binding affinity and good specificity for PDE10A, as well as favorable in vivo pharmacokinetic properties and binding profiles. Our data suggests that [(11)C]TZ1964B is a promising radioligand for in vivo imaging PDE10A in the brain of living subject. Copyright © 2015. Published by Elsevier Inc.
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