S

Brain SPECT imaging is often combined with computed ► Tomography (CT) to provide a detailed structural brain image for overlaying SPECT data.

Resolution

The resolution of SPECT imaging is determined largely by the design of the hardware and software for the gamma camera system. Modern SPECT scanners in general clinical use have resolutions of around 1 cm but special small-animal research SPECT scans, using modified hardware and software for image construction, can achieve resolutions of less than 1 mm (Masdeau and Arbizu 2008; Spanoudaki and Ziegler 2008).

Time Course and Availability

SPECT radionuclides have relatively long ► half-lives, for example the half-life for two widely used radionuclides is about 13 h for 123I compounds and about 6 h for 99mTc compounds. Because of this stability, SPECT ligands can be injected up to several hours before the actual scanning procedure. Some commonly used SPECT radiopharma-ceuticals and their indications are shown in Table 1. It is important to note that the availability of these ligands for human research or clinical applications is determined by the rules of each country, so that not all ligands are available in all regions.

Uses

SPECT therefore has broad applicability in basic research and clinical research, diagnosis, and treatment. Based on the principle that increased regional cerebral neuronal activity is associated with increased blood flow, SPECT perfusion studies can provide indirect information related to local neuronal activity and metabolism. SPECT perfusion studies are used to measure baseline blood flow, blood flow changes associated with task-related activity, or blood flow changes associated with drug effects (Malizia 2006).

SPECT imaging with target molecule-binding radio-pharmaceuticals can be used to measure the baseline levels of target molecules and can measure the influence of experimental manipulations, genetics, and disease states on target molecules. Two useful examples of SPECT methods as applied to human clinical and research conditions include the study of Parkinson's disease and substance abuse disorders.

In ► Parkinson's disease, a neurodegenerative illness characterized by loss of brainstem dopaminergic innervation of the striatum, SPECT imaging has been used to

SPECT Imaging. Table 1. Sample brain SPECT compounds and applications used in psychopharmacology.

Radionuclide

Half-life

Compound

Acronym

Measurement

133Xe

5.24 days

133Xenon

133Xe

rCBF

99™Tc

6.02 h

99mTc-hexamethylpropyleneamineoxime

99mTc-HMPAO

rCBF

99™Tc

6.02 h

99mTc-diethylenetriaminepentaacetic acid

99mTc-DTPA

CSF, brain death

67Ga

78.3 h

67Ga-ethylenediaminetetraacetic acid

67Ga-EDTA

Blood-brain barrier permeability

123i

13.2 h

123Iomazenil

123i-imz

Central type benzodiazepine-receptor binding

123i

13.2 h

123I-2-((2-((dimethylamino)methyl)phenyl) thio)-5-iodophenylamine

123i-adam

Serotonin transporter imaging

123i

13.2 h

123I-ß-carbomethoxy-3-ß-(4-iodophenyl)-tropane

123I-CIT

Dopamine and serotonin transporters

123i

13.2 h

123I-iodobenzamide

123i-ibzm

Dopamine D2 receptor ligand

99mTc

6.02 h

99mTc-TRODAT

99mTc-TRODAT

Dopamine transporter sites

111In

2.83 days

[1n In-DOTA0,D-Phe1,Tyr3] octreotide

111 In-DOTA-TOC

Somatostatin receptor imaging

123i

13.2 h

[123I]5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine

123I-5IA

Nicotinic acetylcholine receptors

123|

13.2 h

6-iodo-2-(4' -dimethylamino-) phenylimidazo[1,2-a]pyridine

123i-impy

ß-amyloid plaque imaging

rCBF relative cerebral blood flow;CSF cerebrospinal fluid. Modified and adapted from Accorsi 2008. Used with permission rCBF relative cerebral blood flow;CSF cerebrospinal fluid. Modified and adapted from Accorsi 2008. Used with permission demonstrate reductions in the levels of the presynaptic ► dopamine transporter (DAT) and increased levels of postsynaptic dopamine receptors (D2 subtype). SPECT may also have utility in monitoring Parkinson's disease progression and assessing the success of treatment interventions. In clinical conditions suggestive of early Parkinson's disease, SPECT assays of dopamine status may aid in diagnosis by determining whether early alterations in the DAT or D2 receptors are consistent with this illness (Booij and Knol 2007). Figure 3 illustrates the difference between a healthy control subject and patient's with Parkinson's disease at different levels of severity. As disease severity worsens, there is near complete absence of detectable DAT binding as measured using the DAT ligand [99mTc] TRO-DAT-1 (Huang et al. 2004).

As reviewed by Volkow and others (Volkow et al. 2003; Felicio et al. 2009), SPECT (and PET) methods are used widely to study the effects of substance abuse and dependence and have contributed greatly to our understanding of drug effects in humans. For example, SPECT has been used to detect drug-induced changes in the ► serotonin transporter, serotonin receptors, and cerebral blood flow following recreational exposure to 3,4-methylenedioxy-methamphetamine (► MDMA; Ecstasy). For multiple drugs of abuse, SPECT imaging has been successful in documenting the effects of drug exposure on receptor and transporter systems (for multiple neurotransmitters, but especially the dopamine system) and on cerebral blood flow. SPECT imaging has also proven critical in documenting the time course of neurotransmitter and blood flow changes associated with acute and chronic drug exposure and following drug withdrawal.

Strengths and Limitations

Strengths of SPECT are considerable. Some SPECT radio-pharmaceuticals are less costly, more easily synthesized, and provide a lower radiation dosage than some PET tracers. This enhances the ease of use and acceptability of SPECT for human psychopharmacological research. Limitations of SPECT include the relatively small number

SPECT Imaging. Fig. 3. SPECT imaging in Parkinson's disease. These images show the utility of SPECT, using [99mTc]TRODAT-1 to measure dopamine transporter (DAT) loss in Parkinson's Disease. The highest signal intensities are shown in red, corresponding to high levels of the DAT. (a) Healthy control subject. The bilaterally symmetric bright red regions are the striatum. (b-f) Represent increasingly severe stages of Parkinson's disease, with progressive loss of striatal DAT binding (From Huang et al. 2004. Used with kind permission of Springer Science + Business Media).

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