![]() ![]() Briefly, for each scan, dynamic blood, metabolite, and tissue data were acquired for 100 min and analyzed with a two-tissue compartment model to derive regional estimates of V T for cerebellum, dorsolateral prefrontal cortex, medial prefrontal cortex, orbito-frontal cortex, subgenual prefrontal cortex, anterior cingulate cortex, temporal cortex, insular cortex, parietal cortex, occipital cortex, medial temporal lobe, and dorsal raphe nuclei. ![]() Data were taken from subject 5 (PET scans 1 and 4) in Martinez et al (2001). administration of 30 mg of the 5HT 1A partial-agonist pindolol. Data Set II: an WAY100635 study in the human brain at baseline and after p.o. Briefly, for each of the four scans, dynamic blood, metabolite and tissue data were acquired for 90 min and analyzed with a two-tissue compartment model to derive regional estimates of V T for cingulate, frontal, temporal, parietal and occipital cortices, cerebellum, hippocampus, striatum, and dorsal raphe nuclei. administration of a 5HT 1A antagonist at doses of 1.5, 10, and 150 μg/kg. To show the application of the modified and extended Lassen plots described in equations (2) and (6) we have applied them to two PET occupancy data sets acquired in vivo with the 5HT 1A radioligand WAY100635 Data Set I: an WAY100635 study in the baboon brain at baseline and 1 h after i.v. We have therefore investigated this phenomenon in this case.Įxamples from In Vivo Positron Emission Tomography Data Sets In general, graphical analyses may lead to noise-induced bias in the parameter estimates if there is correlated noise present in both the x- and y-variables ( Cunningham, 1985 Carson, 1993 Slifstein and Laruelle, 2000). We present a simple variation on the plot presented by Lassen that we have found particularly useful in the visualization and interpretation of drug occupancy studies, together with a generalization of the method applicable under conditions where a true baseline scan in the absence of the drug is not available. This contrasts with the rapid uptake of both the Patlak Plot ( Patlak et al, 1983) and Logan Plot ( Logan et al, 1990) for the analysis of irreversible and reversible PET data and their associated reference tissue derivatives ( Patlak and Blasberg, 1985 Logan et al, 1996). We find it surprising that, to our knowledge, little use of Lassen's plot has been made ( Gjedde and Wong, 2000 Asselin et al, 2003 Pinborg et al, 2007) even with the dramatic increase in the number of occupancy studies being performed with exogenous drugs and the increasing number of targets for which ligands with suitable reference regions do not exist. The principle is, however, equally applicable to heterologous competition between tracer and drug with V Ts derived either from quantitative equilibrium studies or from kinetic compartmental analyses of dynamic studies, under the assumption that there is a steady state of occupancy for the duration of the scan. This approach was originally applied to estimate regional B max and K D for the benzodiazepine receptor ligand, Flumazenil, over a range of drug concentrations, using radiolabeled Flumazenil under steady state conditions. The assumptions were minimal, simply that there is a range of regions with differing target density ( B max), nonspecific binding is homogeneous and occupancy is the same in all regions. In 1995, Lassen et al introduced a plot based on regional changes in V T after drug administration, from which occupancy could be derived despite the absence of a true reference region. It is, however, frequently the case that a suitable reference region, with negligible specific binding, is not available. The BP can be derived from the total volume of distribution of the radioligand ( V T) if an estimate of the volume of distribution of the free plus nonspecifically bound radioligand ( V ND) is available ( Mintun et al, 1984 Innis et al, 2007). The estimation of neuroreceptor occupancy by an exogenous drug using positron emission tomography (PET) is based on the measurement of the fractional decrease in the specific binding potential (BP) of a radioligand after drug administration. ![]()
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