Ronald L. Cowan , Robert Kessler 1Psychiatric Neuroimaging Program, Vanderbilt Addiction Center, Departments of Psychiatry and Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA 2Vanderbilt University School of Medicine, Radiology & Radiological Sciences, Nashville, TN, USA
Single photon emission computed tomography; Single photon emission tomography (SPET); SPET
SPECT is a nuclear imaging method that uses a radioactive tracer (radiopharmaceutical) to measure blood flow or to label brain molecules of interest. The radioactive tracers used in SPECT produce a single photon that is detected by a camera sensitive to photon emissions (gamma camera). SPECT can be used in animal and human research and in human clinical diagnosis to non-invasively assay cerebral blood flow (as an indirect marker of neuronal activity) and cell molecular components of interest (targets) such as neurotransmitter receptors, neu-rotransmitter reuptake transporters, and other proteins of interest. SPECT methods and uses overlap considerably with those of positron emission tomography (► PET), another nuclear imaging method widely used in psycho-pharmacology.
Principles and Role in Psychopharmacology Basic Method
The fundamental principle of SPECT imaging consists of detecting, localizing, and quantifying gamma ray emissions from radiolabeled compounds. Gamma ray emissions are produced when an unstable isotope decays, emitting a photon. The radiolabeled compound is injected intravenously into an animal or human where it circulates throughout the body and to the brain. The photons emitted by the radiolabled compound are then detected with the ► Gamma Camara System. Figure 1 shows a schematic of a SPECT imaging method, and Fig. 2 is an example of a human SPECT imaging system with two gamma cameras that can be positioned to image an area of interest.
SPECT tracers in psychopharmacology are primarily of two types: (1) those that cross the ► blood-brain barrier and distribute nonspecifically in the brain (perfusion radiopharmaceuticals), and (2) those that cross the blood-brain barrier and distribute according to specific molecular targets (target molecule-binding radiopharma-ceuticals).
SPECT perfusion ► radiopharmaceuticals (used to measure blood flow) are compounds that cross the blood-brain barrier and then distribute into the extracellular space in proportion to the blood flow to a region (Masdeu and Arbizu 2008). A successful SPECT perfusion tracer must have the correct lipophilicity properties so that it crosses the blood-brain barrier easily, but it must also have no specific binding to brain components. Once
SPECT Imaging. Fig. 1. SPECT imaging system. (Mettler and Guiberteau 2006, p 26).
SPECT Imaging. Fig. 2. Human SPECT Scanner. A two-camera human SPECT scanner. (► http://www.impactscan. org/images/Philips_Precedence_SPECT-CT.jpg. Picture provided courtesy of Philips Healthcare).
the photon counts are detected by the gamma camera system, the relative cerebral blood flow to an area can be determined. Since local neuronal activity is strongly coupled to cerebral blood flow, SPECT tracers can therefore be used as indirect indicators of changes in local neuronal activity.
unlike SPECT perfusion radiopharmaceuticals, target molecule-binding radiopharmaceuticals must have high
► affinity and specificity for the target molecule. Usually, the affinity for the specific target molecule is at least tenfold greater than the concentration of the target molecule to be imaged. This requires that target molecule-binding radiopharmaceuticals have affinities for their target molecules in the low nanomolar to picomolar range. In addition, these radiotracers must have sufficient lipo-philicity to allow penetrance of the blood-brain barrier, but not so high a lipophilicity as to produce high nonspecific binding.
► Radionuclide. The two most widely used radionuclides in SPECT imaging are technetium (Tc) as [99mTc] and iodine (I) as [123I]. SPECT radionuclides are made primarily by irradiating atoms with charged particles (Leslie and Greenberg 2003; Mettler and Guiberteau 2006). A pharmacological molecule of interest, for example a neu-rotransmitter receptor or reuptake transporter binding li-gand, is then chemically attached to the radionuclide to create the ► Radiopharmaceutical. Because 123I, 99mTc, and other single photon emitting radionuclides are relatively heavy atoms, it is difficult to attach them to small biologically active molecules such as glucose and have such small molecules retain their biological activity. As a result, SPECT radiopharmaceuticals for brain imaging are restricted to molecules with molecular weights of a few hundred, but cannot be too large as they will not pass the blood-brain barrier.
Image construction for SPECT requires the use of a specialized detection system called a gamma camera that uses hardware and software approaches to generate an image that shows the location and intensity of the tracer (Accorsi 2008).
In both SPECT perfusion imaging and SPECT target molecule imaging, mathematical models are used to interpret the results. These models account for the intrinsic properties of the tracer, such as the rate at which the tracer reaches equilibrium in the brain and nonspecific binding of the tracer.
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