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To evaluate the postulated role of extrastriatal D 1  receptors in human cognition and psychopathology requires an accurate and reliable method for quantification of these receptors in the living human brain. [ 11 C]NNC 112 is a promising novel radiotracer for positron emission tomography imaging of the D 1  receptor. The goal of this study was to develop and evaluate methods to derive D 1  receptor parameters in striatal and extrastriatal regions of the human brain with [ 11 C]NNC 112. Six healthy volunteers were studied twice. Two methods of analysis (kinetic and graphical) were applied to 12 regions (neocortical, limbic, and subcortical regions) to derive four outcome measures: total distribution volume, distribution volume ratio, binding potential (BP), and specific-to-nonspecific equilibrium partition coefficient ( k 3 / k 4 ). Both kinetic and graphic analyses provided BP and k 3 / k 4  values in good agreement with the known distribution of D 1  receptors (striatum &gt; limbic regions = neocortical regions &gt; thalamus). The identifiability of outcome measures derived by kinetic analysis was excellent. Time-stability analysis indicated that 90 minutes of data collection generated stable outcome measures. Derivation of BP and k 3 / k 4  by kinetic analysis was highly reliable, with intraclass correlation coefficients (ICCs) of 0.90 ± 0.06 (mean ± SD of 12 regions) and 0.84 ± 0.11, respectively. The reliability of these parameters derived by graphical analysis was lower, with ICCs of 0.72 ± 0.17 and 0.58 ± 0.21, respectively. Noise analysis revealed a noise-dependent bias in the graphical but not the kinetic analysis. In conclusion, kinetic analysis of [ 11 C]NNC 112 uptake provides an appropriate method with which to derive D 1  receptor parameters in regions with both high (striatal) and low (extrastriatal) D 1  receptor density.

journal of cerebral blood flow and metabolism

Measurement of Striatal and Extrastriatal Dopamine D<sub>1</sub> Receptor Binding Potential With [<sup>11</sup>C]NNC 112 in Humans: Validation and Reproducibility

Measurement of Striatal and Extrastriatal Dopamine D1 Receptor Binding Potential With [11C]NNC 112 in Humans: Validation and Reproducibility

Measurement of Striatal and Extrastriatal Dopamine D₁ Receptor Binding Potential With [¹¹C]NNC 112 in Humans: Validation and Reproducibility