Association of dopamine D2/3 receptor binding potential measured using PET and [11C]-(+)-PHNO with post-mortem DRD2/3 gene expression in the human brain
Arkadiusz Komorowski,
Ana Weidenauer,
Matej Murgaš,
Ulrich Sauerzopf,
Wolfgang Wadsak,
Markus Mitterhauser,
Martin Bauer,
Marcus Hacker,
Nicole Praschak-Rieder,
Siegfried Kasper,
Rupert Lanzenberger,
Matthäus Willeit
Affiliations
Arkadiusz Komorowski
Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Ana Weidenauer
Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Matej Murgaš
Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Ulrich Sauerzopf
Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Wolfgang Wadsak
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria
Markus Mitterhauser
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Applied Diagnostics, Vienna, Austria
Martin Bauer
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
Marcus Hacker
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
Nicole Praschak-Rieder
Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Siegfried Kasper
Center for Brain Research, Medical University of Vienna, Vienna, Austria
Rupert Lanzenberger
Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Corresponding author.
Matthäus Willeit
Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Open access post-mortem transcriptome atlases such as the Allen Human Brain Atlas (AHBA) can inform us about mRNA expression of numerous proteins of interest across the whole brain, while in vivo protein binding in the human brain can be quantified by means of neuroreceptor positron emission tomography (PET). By combining both modalities, the association between regional gene expression and receptor distribution in the living brain can be approximated. Here, we compare the characteristics of D2 and D3 dopamine receptor distribution by applying the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and human gene expression data. Since [11C]-(+)-PHNO has a higher affinity for D3 compared to D2 receptors, we hypothesized that there is a stronger relationship between D2/3 non-displaceable binding potentials (BPND) and D3 mRNA expression. To investigate the relationship between D2/3 BPND and mRNA expression of DRD2 and DRD3 we performed [11C]-(+)-PHNO PET scans in 27 healthy subjects (12 females) and extracted gene expression data from the AHBA. We also calculated D2/D3 mRNA expression ratios to imitate the mixed D2/3 signal of [11C]-(+)-PHNO. In accordance with our a priori hypothesis, a strong correlation between [11C]-(+)-PHNO and DRD3 expression was found. However, there was no significant correlation with DRD2 expression. Calculated D2/D3 mRNA expression ratios also showed a positive correlation with [11C]-(+)-PHNO binding, reflecting the mixed D2/3 signal of the radioligand. Our study supports the usefulness of combining gene expression data from open access brain atlases with in vivo imaging data in order to gain more detailed knowledge on neurotransmitter signaling.
