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Post mortem receptor mapping of the human brain Håkan Hall Department of Clinical Neuroscience, Karolinska Institute, Stockholm |
Visualization
of receptors and transporters in the human brain can be achieved with a large
number of techniques. In vivo techniques include PET and SPECT, as well as ex
vivo assays, where the analyses are performed in vitro after in vivo
administration of the compound. In vitro visualization of human brain receptors
and transporters can be performed using a number of techniques, such as
autoradiography, in situ hybridization and immunohistochemistry. In vitro
autoradiography is commonly used for the study of distribution and regional
pharmacology of receptors, in both micro- and macroscopical levels. The present
communication deals with autoradiography using post mortem human whole
hemispheres (whole hemisphere autoradiography, WHA), and the use of this
technique as a tool for the study of receptor distribution in the control and
diseased brain. This technique is especially useful when performing comparisons
with in vivo techniques like PET and SPECT. Radioligand autoradiography with the
same radioligands (however normally with long-lived isotopes in vitro) can
result in high resolution images that are complementary to the PET / SPECT
images.
The
techniques used for WHA will be described in detail. Special emphasis will be
put on the use of different isotopes (3H, 11C, 18F
and 125I) and correlation with in vivo binding using PET and SPECT.
Examples from the work performed at the Karolinska Institutet, Stockholm,
Sweden on receptor and transporter distribution of mainly dopamine (D1,
D2 and D3 dopamine receptors, dopamine transporter) and
serotonin receptor subtypes (5–HT1A, 5–HT1B/D, 5–HT2A,
5–HT4, 5–HT6, 5–HT7 and serotonin
tranpsorter) will be shown.