Measurement of striatal D-2 dopamine receptor density and affinity with [C-11]-raclopride in vivo: A test-retest analysis

Subacute acid long-term stability of measurements of D-2 dopamine receptor density (Bmax), affinity (Kd) was studied with positron emission tomography in eight healthy male volunteers. [C-11]-Raclopride and the transient equi librium method were used to measure D-2 receptor characteristics. The inter val between measurements (scan pairs) was 3 to 7 weeks (subacute) for four subjects and 6 to 11 months (long-term) for four subjects. A test-retest an alysis of quantitative measurements of D-2 receptor Bmax and Kd was compare d with that done on binding potential (BP, Bmax/Kd) measures. In addition, the effect of error in defining the transient equilibrium time (tmax) in th e parameter estimation procedure was explored with simulations. The subacut e test-retest indicates good reproducibility of D-2 receptor density, affin ity, and BP ratio measurements with intraclass correlation coefficients of 0.90, 0.96, and 0.86, respectively. The variability of the measurements aft er 6 to 11 months was slightly higher than that seen in a subacute testing for Kd and more clearly so for binding potential and Bmax. The absolute var iability in Bmax (14.5%) measurements was consistently higher than that of Kd (8.4%) or BP (7.9%) both in subacute and long-term measurements. Simulat ions indicated that the Bmax and Kd estimation procedure is more sensitive to error in the tmax than that for the BP. The results indicate a good over all stability of the equilibrium method with [C-11]raclopride for measuring dopamine D-2 receptor binding characteristics in the striatum. The BP appr oach is more stable than Kd and especially Bmax measurements. Error in defi ning the tmax in particular in the low specific radioactivity scan may be o ne source of greater variability in Bmax versus BP. However, a higher intra individual variability in measurements of the D-2 receptor Bmax also may in clude a component of continuous regulation of this parameter over time. The se methodologic aspects should be considered in the design and interpretati on of longitudinal studies on D-2 dopamine receptor characteristics with [C -11]-raclopride.