Molecular Imaging and Targeted Therapy in Neurology
As the most common motor neurodegenerative disorder, Parkinson’s disease has been the second most common neurodegenerative disorder after Alzheimer’s disease (AD). The prevalence of Parkinson’s disease (PD) is around 1% at age 60 and 4–5% at 85. Bradykine
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17
Qian Xu, Weishan Zhang, and Chuantao Zuo
17.1 Parkinson’s Disease
17.1.1 18F-FDG PET Imaging
As the most common motor neurodegenerative disorder, Parkinson’s disease has been the second most common neurodegenerative disorder after Alzheimer’s disease (AD). The prevalence of Parkinson’s disease (PD) is around 1% at age 60 and 4–5% at 85. Bradykinesia is the most important symptoms in PD, and resting tremor, rigidity, and postural instability are the other three cardinal motor symptoms presented in the disease. Two main neuropathologies of PD are characterized by progressive cell loss of dopaminergic neurons predominately of the ventrolateral part of the pars compacta of the substantia nigra and the presence of Lewy pathology including Lewy bodies (LBs) and Lewy neurites (LNs). As the accurate diagnosis of PD depends on autopsy of substantia nigra, the current clinical diagnosis of PD is decided by the special motor neurologists by assessing the clinical signs and the response to levodopa therapy. However, only 76% of patients thought clinically to have PD prove to have this diagnosis at postmortem. And it is reported that the misdiagnosis rates are as high as 20–30% in early stages. It is necessary and instrumental to utilize more objective method to in vivo explore the underlying mechanisms and make a better diagnosis. Functional neuroimaging methods, such as PET and SPECT with various radioactive tracers (radioligands), can not only provide objectively quantitative assessment but also demonstrate the prompt and patient-based molecular signaling pattern that is essential for the individualized assessment in different points of care. Functional imaging methods that we use widely in PD can currently be divided into investigation of glucose metabolism and investigations of receptor binding.
F-FDG PET imaging has been employed to assess regional cerebral glucose metabolism. Myriads of researches utilized it to quantify presynaptic dopaminergic function indirectly through the measurement of changes in brain metabolism occurring downstream from the nigrostriatal lesion and obtained the specific FDG PET imaging in PD patients that showed regionally increased metabolism in the lentiform nucleus, thalamus, pons, and cerebellum and relatively decreased metabolism in the lateral frontal, paracentral, and parietal association areas. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy in differentiating PD from other Parkinsonism such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). From a single case basis, FDG PET was possibly considered to differentiate patients with presumed PD, MSA, PSP, CBGD, and healthy controls with an accuracy of about 90% based on a retrospective analysis of the scan data. As FDG PET imaging can particularly measures the local synaptic activity and biochemical maintenance processes which dominate cerebral function at rest state, the effects of pathology in neurodegenerative diseases on these functions have a greater influence on region
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