from Part II - Neuroimaging in neurodegeneration
Published online by Cambridge University Press: 04 August 2010
Introduction
Neurodegenerative diseases, particularly those affecting the basal ganglia and related pathways, are often associated with abnormal activity of nigrostriatal dopaminergic projections. The integrity of this system can be assessed by neuroimaging methods utilizing radioligands that bind to pre or postsynaptic components. By contrast, the functional organization of the basal ganglia and its projections can be assessed by imaging regional cerebral blood flow and metabolism as measures of neural activity. Single photon and positron emission tomographic imaging (SPECT and PET) have been applied in studies of network activity. While these studies have relied mainly upon PET imaging in the resting state and during brain activation, SPECT and magnetic resonance techniques have also been used for this purpose. In this chapter, we will review the development of PET and SPECT techniques as markers of neurodegenerative processes specifically to assess rates of disease progression and the effects of novel therapeutic interventions.
Presynaptic dopaminergic function
Dopamine transporter imaging
The dopamine transporter (DAT) enables the release and reabsorption of dopamine in the nigrostriatal intersynaptic cleft. Different radiotracers, mostly cocaine analogues, have been developed to quantify striatal DAT binding as an objective marker of the integrity of presynaptic nigrostriatal dopamine terminals (Wilson et al., 1996; Ma et al., 2002) (Fig. 20.1). DAT imaging can be implemented with a variety of radiotracers using either SPECT or PET techniques. The major SPECT compounds in current use include [123I]-2β-carbomethyl-3β-(4-iodophenyl) tropane (βCIT) and its fluoropropyl derivative [123I] FPCIT, [123I]-Altropane, [123I]-(N)-(3-io dopropen-2-yl)-2β-carbomethoxy-3β-(4-chlorophenyl) tropane (IPT), and [99mTc]-2β-((N, N′-bis(2-mercaptoethyl)ethylene diamino)methyl), 3β-(4-chlorophenyl)tropane) (TRODAT).
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