Quantitative evaluation of changes in binding potential with a simplified reference tissue model and multiple injections of [¹¹C]raclopride

Positron emission tomography (PET) with [¹¹C]raclopride is widely used to investigate temporal changes in the dopamine D₂ receptor system attributed to the dopamine release. The simplified reference tissue model (SRTM) can be used to determine the binding potential (BP_ND) value using the time-activity curve (TAC) of the reference region as input function. However, in assessing temporal changes in BP_ND using the SRTM, multiple [¹¹C]raclopride PET scans are required, and a second scan must be performed after the disappearance of the [¹¹C]raclopride administered in the first scan. In this study, we have developed an extended multiple-injection SRTM to estimate the BP_ND change, from a single PET scan with multiple injections of [¹¹C]raclopride, and we have validated this approach by performing numerous simulations and studies on monkeys. In the computer simulations, TACs were generated for dual injections of [¹¹C]raclopride, in which binding conditions changed during the scans, and the BP_ND values before, and after, the second injection were estimated by the proposed method. As a result, the reduction in BP_ND was correlated, either with the integral of released dopamine, or with the administered mass of raclopride. This method was applied to studies on monkeys, and was capable of determining two identical BP_ND values when there were no changes in binding conditions. The BP_ND after the second injection decreased when binding conditions changed due to an increase in administered raclopride. An advantage of the proposed method is the shortened scan period for the quantitative assessment of the BP_ND change for neurotransmitter competition studies.