Graphical Analysis of Reversible Radioligand Binding from Time—Activity Measurements Applied to [N-¹¹C-Methyl]-(−)-Cocaine PET Studies in Human Subjects

Abstract

Summary: A graphical method of analysis applicable to ligands that bind reversibly to receptors or enzymes re quiring the simultaneous measurement of plasma and tis sue radioactivities for multiple times after the injection of a radiolabeled tracer is presented. It is shown that there is a time tt after which a plot of nROI(t')dt'/ROI(t) versus J�Cp(t')dt' IROI(t) (where ROI and Cp are functions of time describing the variation of tissue radioactivity and plasma radioactivity, respectively) is linear with a slope that corresponds to the steady-state space of the ligand plus the plasma volume, Vp. For a two-compartment model, the slope is given by >.. + Vp, where >.. is the partition coefficient and the intercept is -l I[k2(l + Vp/>.. »). For a three-compartment model, the slope is >"(1and the intercept is -{(l + BmaxlKd)lk2

Quantitative Analysis for Estimating Binding Potential of the Peripheral Benzodiazepine Receptor with [11C]DAA1106

“…Graphical Analysis Method: Graphical analysis (GA) yields DV by arterial input function and the tissue timeactivity curve (TAC) (Logan et al, 1990). Parameters are estimated from the equation…”

Evaluation of Dopamine D-2 Receptor Occupancy by Clozapine, Risperidone, and Haloperidol In Vivo in the Rodent and Nonhuman Primate Brain Using 18F-Fallypride

“…This index was measured by using the distribution volume method (DV) of 18 F-fallypride in each brain region (Logan et al 1990) as well as the distribution volume ratio method (DVR) using the cerebellum as a reference region (Logan et al 1996) and are described below.…”

“…Method A: Distribution Volume (DV) (Logan et al 1990). This is a multiple time graphic method of analysis that yields a parameter representing the total (free, nonspecific, and specifically bound 18 F-fallypride) distribution volume (DV) of the radioligand in a given region and is equal to K 1 /k 2 (1 ϩ NS ϩ B Ј max /K D ), where K 1 and k 2 are the plasma-to-tissue and tissue-to-plasma rate constants, B Ј max is the concentration of available receptor sites, NS is the ratio of binding constants for nonspecific binding of the radiotracer, and K D is the equilibrium dissociation rate constant (Logan et al 1990;Volkow et al 1999).…”

“…This is a multiple time graphic method of analysis that yields a parameter representing the total (free, nonspecific, and specifically bound 18 F-fallypride) distribution volume (DV) of the radioligand in a given region and is equal to K 1 /k 2 (1 ϩ NS ϩ B Ј max /K D ), where K 1 and k 2 are the plasma-to-tissue and tissue-to-plasma rate constants, B Ј max is the concentration of available receptor sites, NS is the ratio of binding constants for nonspecific binding of the radiotracer, and K D is the equilibrium dissociation rate constant (Logan et al 1990;Volkow et al 1999). Using a region such as the cerebellum and applying the method as outlined by Volkow et al 1999, the percentage occupancy is calculated as (DVcont /DV cer Ϫ 1)-(DV drug /DV cer Ϫ 1)/(DV cont /DV cer Ϫ 1) ϫ 100 where DV cont and DV drug are the distribution vol-umes in a region-of-interest (caudate, putamen, thalamus, frontal cortex, or temporal cortex) in the control and drug challenge study, and DV cer is a predetermined estimate of the free plus nonspecific distribution volume, K 1 /k 2 (1ϩNS) calculated from compartmental modeling of the cerebellum in the control studies; a value of 0.97 for DV cer was used.…”

Evaluation of Four Pyridine Analogs to Characterize 6-OHDA-Induced Modulation of mGluR5 Function in Rat Brain Using microPET Studies

“…The severity of the lesion was determined by PET imaging of DA transporter binding using [ 11 C]CFT, a selective and sensitive ligand for DA transporter (Brownell et al, 1996). After PET imaging with mGluR5 ligands and [ 11 C]CFT binding potential images were processed using a modified graphical method of Logan (Logan et al, 1990(Logan et al, , 1996Logan, 2000). In addition, representative regions of interests (ROIs) were drawn to the left and right brain areas on the original images of activity distribution.…”