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Figure 6.1. PET scan in this 74-year-old female patient with mild DAT (MMSE score 21/30) shows highest retention of the styrylbenzene [11C]SB-13, a radiotracer for Aft(1-40) amyloid aggregates in the left cerebral cortex, particularly in frontal and temporo-parietal association cortices. (Courtesy of Drs. Alan A. Wilson, N. Paul, L.G. Verhoeff, and Sylvain Houle, PET Centre, CAMH, Toronto, Ont.) See ftp site for color image.

anyloid plaques (AP) in the brains of living Alzheimser's disease patients. Similarly, the styrylbenzene [11C]SB-13, is a promising radiotracer for Aft(1-40) amyloid aggregates in the cerebral cortex of DAT patients (Fig. 6.1). This noninvasive technique for monitoring AP and NFT development is expected to facilitate diagnostic assessment of patients with Alzheimer's disease and assist in response-monitoring during experimental treatments.

NEUROTRANSMITTER IMAGING STUDIES

Neurotransmitter imaging studies employ receptor-specific ligands in a variety of different experimental protocols. For example, the two PET ligands [11C]raclopride and [11C]N-methylspiperone both bind to dopamine D2 receptors, although [11C]raclopride is thought to bind only to the monomeric form of the D2 receptor whereas [11C]N-methylspiperone is thought to bind to both the monomeric and the dimeric forms of the receptor. In addition, D2 receptors, although usually localized to the cell membrane, may also be internalized in cell vesicles. While [11C]raclopride is thought to bind only the membrane-bound receptors, [11C]N-methylspiperone may also bind to internalized receptors because of its greater lipophilicity. As should be evident from this example, one ligand may be preferable to another depending on the specific question to be examined in a study. Data acquired using one ligand may not simply be extrapolated to another. Therefore, knowledge of both the ligands and the methodological approaches is necessary in order to avoid type I errors and interpretational mistakes. A brief overview of the ligands and methodological approaches used most frequently in psychiatric neuroimaging studies can be found in Tables 6.1 and 6.2.

TABLE 6.1. Commonly Used Radiotracers for Neurotransmitter Imaging with PET and SPECT

SPECT-Ligand

Application

PET-Ligand

[123I]ß-CIT

DAT and 5-HTT

[nC]cocaine [n C]methylphenidate

[123I]nor-ß-CIT

5-HTT

[123I]iodoketanserine

5-HT2 receptors

[18F]setoperone [18F]altanserin

5-HT1A receptors

[11C]WAY-100.635

[123I]IBF [123I]IBZM

Striatal D2 receptors

[nC]raclopride [nC]N-methylspiperone

[123I]epidepride

Extrastriatal D2 receptors

[nC]epidepride [nC]FLB-457

[123I]iomazenil

GABAa receptor

[nC]flumazenil

TABLE 6.2. Applications of Functional Neuroimaging in Neuropsychiatry Research

Method

Radioligand

Radioligand in tracer dose application

Competition of a tracer with a drug for binding sites Simultaneous use of a drug and a tracer with affinity to a different transmitter system [3H]H2O, [123I]HMPAO, or [18F]FDG Radiolabeled enzyme substrates

Application

Distribution in brain and other organs Concentration of binding sites in brain and other tissue (= binding potential) Relative receptor occupancy of the drug

Effect of the drug on other neurotransmitter systems

Regional cerebral blood flow or metabolism Indirect determination of enzyme activity or cerebral metabolism

The two best investigated neurotransmitter systems in psychiatry are the serotonin and dopamine systems, followed by the noradrenergic and cholinergic systems, and to a much lesser extent also the glutamatergic, GABAergic, and gycinergic systems. In addition, the opioid and endogenous cannabinoid systems are sometimes also of interest for psychiatric neuroimaging studies, primarily for investigations into the neurobiology of substance use and abuse.

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