Comparison of Methods for Analysis of Clinical [¹¹C]Raclopride Studies

Abstract

Five different methods for the estimation of the binding potential, a measure of Bmax/Kd, of [11C]raclopride in human striatum were compared using data from a dose ranging study of the neuroleptic CP-88,059-01. Binding potential was estimated indirectly, from distribution volumes in striatum and cerebellum, using both single- and two-tissue compartment models with a metabolite-corrected plasma curve as input function. The two-tissue compartment model was also used for a direct estimate of the binding potential. In addition, a direct estimate was obtained from the reference tissue compartment model using the cerebellum as indirect input function. Finally, an estimate of binding potential was calculated from the ratio of striatum over cerebellum counts at late times after injection. The estimates of striatum binding potential from all methods, except the direct determination using a two-tissue compartment model with metabolite-corrected plasma input function, correlated with each other. Use of an average metabolite correction resulted in only a small reduction in accuracy in this series of normal subjects. The reference tissue model provided estimates of the binding potential with the same sensitivity for detecting changes as those methods that required a metabolite-corrected plasma input function. This indicates that for routine analysis of clinical [11C]raclopride studies, no arterial cannulation is required. The range of normal values was significantly less variable with the reference tissue method than when simple striatum-to-cerebellum ratios were used.

Evaluation of Reference Tissue Models for the Analysis of [11C](R)-PK11195 Studies

“…Indirect plasma input model with two target and one reference tissue compartments (VD 2T1R ). G. Indirect plasma input model with two target and two reference tissue compartments (VD 2T2R ) (Lammertsma et al, 1996a). …”

Quantification of GABAA receptors in the rat brain with [123I]Iomazenil SPECT from factor analysis-denoised images

“…Dashed line represents the minimal duration of acquisition required to obtain stable BP ND estimations. the reference region, corresponds to the binding potential of the tracer [24]. Previously, Millet et al [22] established the reliability of binding parameter estimations analyzing delayed activity acquired between SPECT scans for [ 123 I]IMZ binding quantification in humans.…”

“…Different model configurations were employed for estimation of volume of distribution (V T ) and binding potential (BP F and BP ND ) [31] with the PMOD software: (1) a one-tissue compartment model (1TC), (2) a two-tissue compartment model with (2TC c ) and without (2TC) a constrained K 1 /k 2 ratio value [20], (3) the two-step Simplified Reference Tissue Model described by Wu and Carson [16] (SRTM2) and the (4) Logan graphical analysis [32] using the pons as reference region. In addition, (5) delayedactivity analysis was performed by normalizing the average activity in each VOI to the activity in the pons [24].…”

“…More precisely, the purpose of this study is to evaluate the accuracy and the robustness of the estimation of binding parameters of [ 123 I]Iomazenil across different anatomical structures of the rat brain, using three approaches: a version of the Simplified Reference Tissue Model (SRTM2 [16]), Logan graphical analysis [18] and analysis of delayed activity [22][23][24]. Results obtained with these approaches were compared to the results of kinetic analysis with a one-and a two-tissue compartment model (1TC and 2TC) using plasma-derived input function.…”

Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET: Dopamine Movies of Cigarette Smoking

“…A parametric image is a map of a given tracer kinetic model parameter evaluated at every voxel in the object (i.e., the brain). Application of conventional models such as SRTM 38,39 or the one- or two-tissue compartment model yields parametric images of Ri, the regional flow parameter, or BP, the regional binding potential value. Both of these parameters are physiological constants that are believed to represent processes that are in steady state.…”