Low convergent validity of [C]raclopride binding in extrastriatal brain regions: A PET study of within-subject correlations with [C]FLB 457.

Dopamine D2 receptors (D2-R) in extrastriatal brain regions are of high interest for research in a wide range of psychiatric and neurologic disorders. Pharmacological competition studies and test-retest experiments have shown high validity and reliability of the positron emission tomography (PET) radioligand [C]FLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centers. Instead, the medium affinity radioligand [C]raclopride, which has been extensively validated for quantification of D2-R in the high-density region striatum, has been applied also in studies on extrastriatal D2-R. Recently, the validity of this approach has been questioned by observations of low occupancy of [C]raclopride in extrastriatal regions in a pharmacological competition study with quetiapine. Here, we utilise a data set of 16 healthy control subjects examined with both [C]raclopride and [C]FLB 457 to assess the correlation in binding potential (BP) in extrastriatal brain regions. BP was quantified using the simplified reference tissue model with cerebellum as reference region. The rank order of mean regional BP values were similar for both radioligands, and corresponded to previously reported data, both post-mortem and using PET. Nevertheless, weak to moderate within-subject correlations were observed between [C]raclopride and [C]FLB 457 BP extrastriatally (Pearson's R: 0.30-0.56), in contrast to very strong correlations between repeated [C]FLB 457 measurements (Pearson's R: 0.82-0.98). In comparison, correlations between repeated [C]raclopride measurements were low to moderate (Pearson's R: 0.28-0.75). These results are likely related to low signal to noise ratio of [C]raclopride in extrastriatal brain regions, and further strengthen the recommendation that extrastriatal D2-R measures obtained with [C]raclopride should be interpreted with caution.