Validation of the reference tissue model for estimation of dopaminergic D2-like receptor binding with [18F](N-methyl)benperidol in humans

Abstract

Positron emission tomography measurements of dopaminergic D2-like receptors may provide important insights into disorders such as Parkinson's disease, schizophrenia, dystonia and Tourette's syndrome. The positron emission tomography (PET) radioligand [18F](N-methyl)benperidol ([18F]NMB) has high affinity and selectivity for D2-like receptors and is not displaced by endogenous dopamine. The goal of this study is to evaluate the use of a graphical method utilizing a reference tissue region for [18F]-NMB PET analysis by comparisons to an explicit three-compartment tracer kinetic model and graphical method that use arterial blood measurements. We estimated binding potential (BP) in the caudate and putamen using all three methods in 16 humans and found that the three-compartment tracer kinetic method provided the highest BP estimates while the graphical method using a reference region yielded the lowest estimates (P<.0001 by repeated-measures ANOVA). However, the three methods yielded highly correlated BP estimates for the two regions of interest. We conclude that the graphical method using a reference region still provides a useful estimate of BP comparable to methods using arterial blood sampling, especially since the reference region method is less invasive and computationally more straightforward, thereby simplifying these measurements.

Figure 1

Representative time-activity data from striatum (average of caudate and putamen data) and cerebellum regions. Gray triangles represent striatal values; white diamonds represent cerebellar values. The solid lines are the two-(gray line) and three-compartment (black line) model fits for the cerebellum and striatum, respectively, using the arterial plasma activity (corrected for the presence of labeled metabolites) as the input function.

Figure 2

DVR graphical analysis of the time activity data from the striatum and cerebellum. C_ROI (t) and C_REF(t) represent the radioactivity in the receptor region of interest and the reference region at time t.

Figure 3

Correlational scatter plot for striatal BP estimates obtained from Method 2 (black triangles) and Method 3 (white triangles) as function of estimates obtained with Method 1 (solid line is regression line for Method 2, broken line is regression for Method 3).