PET Radiopharmaceuticals for Alzheimer’s Disease and Parkinson’s Disease Diagnosis, the Current and Future Landscape

Abstract

Ironically, population aging which is considered a public health success has been accompanied by a myriad of new health challenges, which include neurodegenerative disorders (NDDs), the incidence of which increases proportionally to age. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common, with the misfolding and the aggregation of proteins being common and causal in the pathogenesis of both diseases. AD is characterized by the presence of hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFTs), and senile plaques the main component of which is β-amyloid peptide aggregates (Aβ). The neuropathological hallmark of PD is α-synuclein aggregates (α-syn), which are present as insoluble fibrils, the primary structural component of Lewy body (LB) and neurites (LN). An increasing number of non-invasive PET examinations have been used for AD, to monitor the pathological progress (hallmarks) of disease. Notwithstanding, still the need for the development of novel detection tools for other proteinopathies still remains. This review, although not exhaustively, looks at the timeline of the development of existing tracers used in the imaging of Aβ and important moments that led to the development of these tracers.

Amyloid β-binding Bifunctional Chelators with Favorable Lipophilicity for 64Cu PET Imaging in Alzheimer’s Disease

“…To date, three compounds have been approved by the US Food and Drug Administration (FDA) for amyloid imaging: the benzothiazole derivative 18 F-Flutemetamol (Vizamyl), the stilbene derivatives 18 F-Florbetaben (Neuraceq) and 18 F-Florbetapir (Amyvid). [10][11][12][13] However, the relative short half-lives and the necessity of covalent incorporation of the 11 C and 18 F radionuclides have limited the widespread clinical usage of these imaging probes. 14 By comparison, the radionuclide 64 Cu has an optimal half-life of 12.7 hours, and its well established coordination chemistry allows for easy conjugation with the biologically relevant molecules.…”

“…6H) 13. C NMR (126 MHz, CDCl3) δ 172.17, 154.38, 148.61, 134.99, 130.50, 127.29, 126.47, 125.02, 122.91, 121.73, 110.10, 63.04, 60.75, 60.21, 56.53, 52.95, 29.95, 14.48.…”

Dopamine transporter imaging in neurodegenerative movement disorders: PET vs. SPECT

“…A biomarker directly representing the underlying pathophysiology would be ideal, such as in vivo measurement of misfolded α-synuclein, as found in post-mortem PD studies. However, at present, there is no available radioligand for imaging α-synuclein [2]. In vivo imaging of dopamine transporter (DAT) availability in the basal ganglia provides a measure of pre-synaptic dopaminergic integrity and function, and, currently, represents a practical indirect biomarker of PD.…”

Sensors for Cryogenic Isotope-Separation Column

“…Starting from the natural abundance of the isotope of interest, during the separation process it is possible to increase the isotope concentration to a desired level. Various chemical compounds based on enriched ( 13 C) have a broad field of application [ 1 ]: Applications in medical fields: in clinical studies, differential diagnosis of multiple diseases, state of illness judgment, treatment evaluation, research on organ function and development of new drugs [ 2 ], such as PET diagnosis [ 3 ], 13 C-urea breath test [ 4 ], tumor therapy (boron neutron capture therapy) research on drugs [ 5 ], etc. ; Applications in life sciences fields: in the spectrum research of the structure and function of protein species by nuclear magnetic resonance (NMR) and mass spectrometer (MS), including isotope-coded affinity tag testing method (ICATTM), stable isotope labeled amino acid cell cultivation (SILAC), absolute quantification protein analysis method (AQUATM) [ 6 ]; Applications in energy metabolism: in sports medicine, child nutrition, food nutrition, weight loss and diet for astronaut using he-isotope tracing method [ 7 ]; Applications in agricultural scientific research fields: in the research of plant physiology and biochemistry, nutrition of soil and plant, plant protection, the improvement of rice, flower, agricultural products and other crops, nitrogen cycle of grassplot [ 8 ]; Applications in the research of environmental science: monitoring of ecosystem pollution, determining of the length of food chains, ascertaining the pollutant sources in air and water and defining the distribution area of plant [ 9 , 10 ]; Applications in analysis and testing: in the testing of food [ 11 ], pesticide residue analysis [ 12 ], drug and excitant, heroin testing [ 13 ], also in the research of geology, geochemistry, paleontology and ecology [ 14 , 15 ].…”

“…Applications in medical fields: in clinical studies, differential diagnosis of multiple diseases, state of illness judgment, treatment evaluation, research on organ function and development of new drugs [ 2 ], such as PET diagnosis [ 3 ], 13 C-urea breath test [ 4 ], tumor therapy (boron neutron capture therapy) research on drugs [ 5 ], etc. ;…”