Recent developments on PET radiotracers for TSPO and their applications in neuroimaging.
AD, Alzheimer's disease
ALS, amyotrophic lateral sclerosis
AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
ANT, adenine nucleotide transporter
Am, molar activities
BBB, blood‒brain barrier
BMSC, bone marrow stromal cells
BP, binding potential
BPND, non-displaceable binding potential
BcTSPO, Bacillus cereus TSPO
CBD, corticobasal degeneration
CNS disorders
CNS, central nervous system
CRAC, cholesterol recognition amino acid consensus sequence
DLB, Lewy body dementias
EP, epilepsy
FTD, frontotemporal dementia
HAB, high-affinity binding
HD, Huntington's disease
HSE, herpes simplex encephalitis
IMM, inner mitochondrial membrane
KA, kainic acid
LAB, low-affinity binding
LPS, lipopolysaccharide
MAB, mixed-affinity binding
MAO-B, monoamine oxidase B
MCI, mild cognitive impairment
MDD, major depressive disorder
MMSE, mini-mental state examination
MRI, magnetic resonance imaging
MS, multiple sclerosis
MSA, multiple system atrophy
Microglial activation
NAA/Cr, N-acetylaspartate/creatine
Neuroinflammation
OCD, obsessive compulsive disorder
OMM, outer mitochondrial membrane
P2X7R, purinergic receptor P2X7
PAP7, RIa-associated protein
PBR, peripheral benzodiazepine receptor
PCA, posterior cortical atrophy
PD, Parkinson's disease
PDD, PD dementia
PET, positron emission tomography
PKA, protein kinase A
PRAX-1, PBR-associated protein 1
PSP, progressive supranuclear palsy
Positron emission tomography (PET)
PpIX, protoporphyrin IX
QA, quinolinic acid
RCYs, radiochemical yields
ROS, reactive oxygen species
RRMS, relapsing remitting multiple sclerosis
SA, specific activity
SAH, subarachnoid hemorrhage
SAR, structure–activity relationship
SCIDY, spirocyclic iodonium ylide
SNL, selective neuronal loss
SNR, signal to noise ratio
SUV, standard uptake volume
SUVR, standard uptake volume ratio
TBAH, tetrabutyl ammonium hydroxide
TBI, traumatic brain injury
TLE, temporal lobe epilepsy
TSPO
TSPO, translocator protein
VDAC, voltage-dependent anion channel
VT, distribution volume
d.c. RCYs, decay-corrected radiochemical yields
dMCAO, distal middle cerebral artery occlusion
fP, plasma free fraction
n.d.c. RCYs, non-decay-corrected radiochemical yields
p.i., post-injection
Journal
Acta pharmaceutica Sinica. B
ISSN: 2211-3835
Titre abrégé: Acta Pharm Sin B
Pays: Netherlands
ID NLM: 101600560
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
17
04
2020
revised:
15
07
2020
accepted:
29
07
2020
entrez:
1
3
2021
pubmed:
2
3
2021
medline:
2
3
2021
Statut:
ppublish
Résumé
The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.
Identifiants
pubmed: 33643818
doi: 10.1016/j.apsb.2020.08.006
pii: S2211-3835(20)30689-4
pmc: PMC7893127
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
373-393Informations de copyright
© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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