Chapter 51 - Measurement of [ 11 C]Radopride Binding Using a Bolus plus Infusion Protocol

The ratio of basal ganglia to cerebellar uptake of [ 11 C]-raclopride is often used as an index of dopamine D 2 receptor density. This chapter describes a bolus plus constant infusion technique and a data analysis approach that provides reliable estimates of the bound-to-free radioligand ratio. The technique does not require arterial blood sampling or correction for metabolites and protein binding. This method is first developed by computer simulation then it is applied to positron emission tomography studies of 12 control subjects and to 15 receptor occupancy studies. A nonlinear curve-fitting method is used to obtain the free and bound time–activity curves. Then the differential equation is solved by describing the transport of radioligand between the free and bound compartments, but without assuming equilibrium conditions. Because of this, the data analysis technique applies equally well to bolus injection studies. Computer simulations indicate that the free receptor index obtained with the method presented in this chapter is not sensitive to changes in cerebral blood flow when applied to both the bolus and the bolus plus infusion methods. The bolus plus infusion is a simple and reliable technique for clinical research.