TY - CHAP
T1 - Development of brain PET imaging agents
T2 - Strategies for imaging neuroinflammation in Alzheimer's disease
AU - Janssen, Bieneke
AU - Mach, Robert H.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019
Y1 - 2019
N2 - Neuroinflammation is thought to play a key role in the development and progression of neurodegenerative diseases such as Alzheimer's disease. Positron emission tomography (PET) is an in vivo imaging technique capable of studying the biochemical processes which provide the molecular basis of disease. PET imaging of neuroinflammation, which is characterized by the activation of glial cells in the central nervous system (CNS), has been traditionally studied using radiotracers targeting the translocator protein 18 kDa (TSPO). However, limitations in the properties of PET radiotracers for imaging the TSPO has led to the search for alternative strategies for imaging neuroinflammation. The current review presents the current status of PET radiotracers for imaging the TSPO, and describes alternative biological targets that have gained interest for imaging of microglial activation over recent years. These include cannabinoid receptor type-2, cyclooxygenase-2, the P2X7 receptor, CSF1R and reactive oxygen species and some promising radiotracers for these targets. Although a lot of advances have been made in the field of imaging neuroinflammation, current radiotracers all target the pro-inflammatory (M1) phenotype of activated microglia, since the number of known biological targets specific for the anti-inflammatory (M2) phenotype, is still limited. In spite of these limitations, PET imaging studies comparing the temporal relationship between Aβ plaque formation, microglial activation, and the formation of tau-based neurofibrillary tangles would provide valuable information on the “neuroinflammatory hypothesis” of neurodegeneration. The development of a suitable radiotracer for imaging the anti-inflammatory, M2 microglia would represent a great advance in imaging neuroinflammation since this would allow for imaging of the dynamics of microglial activation in different diseases.
AB - Neuroinflammation is thought to play a key role in the development and progression of neurodegenerative diseases such as Alzheimer's disease. Positron emission tomography (PET) is an in vivo imaging technique capable of studying the biochemical processes which provide the molecular basis of disease. PET imaging of neuroinflammation, which is characterized by the activation of glial cells in the central nervous system (CNS), has been traditionally studied using radiotracers targeting the translocator protein 18 kDa (TSPO). However, limitations in the properties of PET radiotracers for imaging the TSPO has led to the search for alternative strategies for imaging neuroinflammation. The current review presents the current status of PET radiotracers for imaging the TSPO, and describes alternative biological targets that have gained interest for imaging of microglial activation over recent years. These include cannabinoid receptor type-2, cyclooxygenase-2, the P2X7 receptor, CSF1R and reactive oxygen species and some promising radiotracers for these targets. Although a lot of advances have been made in the field of imaging neuroinflammation, current radiotracers all target the pro-inflammatory (M1) phenotype of activated microglia, since the number of known biological targets specific for the anti-inflammatory (M2) phenotype, is still limited. In spite of these limitations, PET imaging studies comparing the temporal relationship between Aβ plaque formation, microglial activation, and the formation of tau-based neurofibrillary tangles would provide valuable information on the “neuroinflammatory hypothesis” of neurodegeneration. The development of a suitable radiotracer for imaging the anti-inflammatory, M2 microglia would represent a great advance in imaging neuroinflammation since this would allow for imaging of the dynamics of microglial activation in different diseases.
KW - Cannabinoid receptor type 2
KW - Colony stimulating factor 1 receptor
KW - Cyclooxygenase-2
KW - Microglia
KW - Microglial activation
KW - Neuroinflammation
KW - P2X receptor
KW - Positron emission tomography
KW - Reactive oxygen species
KW - Translocator protein 18 kDa
UR - http://www.scopus.com/inward/record.url?scp=85064935774&partnerID=8YFLogxK
U2 - 10.1016/bs.pmbts.2019.04.005
DO - 10.1016/bs.pmbts.2019.04.005
M3 - Chapter
C2 - 31481170
AN - SCOPUS:85064935774
SN - 9780128183618
T3 - Progress in Molecular Biology and Translational Science
SP - 371
EP - 399
BT - Brain Imaging
A2 - Becker, James T.
A2 - Cohen, Ann D.
PB - Elsevier B.V.
ER -