Similarity and Robustness of PET and SPECT Binding Parameters for Benzodiazepine Receptors

Abstract

The single photon emission computed tomography (SPECT) radiotracer [123I]iomazenil is used to assess benzodiazepine receptor binding parameters. These measurements are relative indices of benzodiazepine receptor concentration (B'max). To evaluate the ability of such indices in accurately accessing the B'max the authors compared them with absolute values of B'max, measured using positron emission tomography (PET). The authors performed SPECT, PET, and magnetic resonance imaging (MRI) studies on a group composed of seven subjects. For SPECT studies, the authors administered a single injection of [123I]iomazenil and estimated the total and specific distribution volumes (DV(T SPECT), DV(S SPECT)) and the binding potential (BP) using unconstrained (BP(SPECT)) and constrained (BP(C SPECT)) compartmental models. For PET studies, the authors used a multiinjection approach with [11C]flumazenil and unlabeled flumazenil to estimate absolute values of receptor concentration, B'max, and some other binding parameters. The authors studied the correlation of different binding parameters with B'max. To study the robustness of the binding parameter measurements at the pixel level, the authors applied a wavelet-based filter to improve signal-to-noise ratio of time-concentration curves, and the calculated kinetic parameters were used to build up parametric images. For PET data, the B'max and the DV(PET) were highly correlated (r = 0.988). This confirms that it is possible to use the DV(PET) to access benzodiazepine receptor density. For SPECT data, the correlation between DV(SPECT) estimated using a two- and three-compartment model was also high (r = 0.999). The DV(T SPECT) and BP(C SPECT) parameters estimated with a constrained three-compartment model or the DV(T''SPECT) parameter estimated with a two-compartment model were also highly correlated to the B'max parameter estimated with PET. Finally, the robustness of the binding parameters allowed the authors to build pixel-by-pixel parametric images using SPECT data.

Tobacco smoking interferes with GABA A receptor neuroadaptations during prolonged alcohol withdrawal

“…Thirteen rhesus monkeys were imaged with [ 11 C]flumazenil and positronemission tomography (PET) to image GABA A receptor availability at baseline-that is, when drug naïve-and then up to three times during alcohol withdrawal. [ 11 C]flumazenil and [ 123 I]iomazenil both measure cortical GABA A receptors, and the outcome measures are highly correlated (19,20). One group of animals (n = 7) consumed only alcohol for up to 20 wk (alcoholonly group) before alcohol withdrawal, and a separate group of animals (n = 6) consumed alcohol and nicotine for up to 20 wk and then continued to consume nicotine over the course of alcohol withdrawal (alcohol + nicotine group).…”

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

“…Obviously, performing scans of minimal duration, employing a model that requires no blood sampling and yet obtaining accurate parameters is a critical factor for the success of clinical and preclinical experiments. All these questions have been thoroughly assessed in human and other primate studies regarding kinetic, graphical and equilibrium analyses [7,20,22,23,33,[40][41][42]. Nevertheless, no study on rodent GABA A quantification with SPECT exists.…”

“…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. In this study, we performed this type of analysis for consequent frames of 10 or 20 min starting from the 40th minute of acquisition and we concluded that activity from an image 50-70 min postinjection provides the parameters that best correlate with parameters obtained with SRTM2.…”

“…In the 2TC, the BP F is obtained by the value of k 3 /k 4 , i.e. the ratio of tracer delivery to tracer efflux from the compartment corresponding to the specific binding to receptors [22]. In this form, parameters resulting from 2TC tend to have an important inter-correlation, leading to diminished identifiability and aberrant BP ND values associated to large standard errors in certain VOIs [22,33].…”

“…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.…”