Recent developments on PET radiotracers for TSPO and their applications in neuroimaging

• Published in: Acta pharmaceutica Sinica. B Vol. 11; no. 2; pp. 373 - 393
• Main Authors: Zhang, Lingling, Hu, Kuan, Shao, Tuo, Hou, Lu, Zhang, Shaojuan, Ye, Weijian, Josephson, Lee, Meyer, Jeffrey H., Zhang, Ming-Rong, Vasdev, Neil, Wang, Jinghao, Xu, Hao, Wang, Lu, Liang, Steven H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2021; Elsevier
• Subjects: CNS disorders; Microglial activation; Neuroinflammation; Positron emission tomography (PET); Review; TSPO; AMPA; BBB; ALS; MDD; dMCAO; RCYs; QA; TSPO; TBI; BPND; HSE; NAA/Cr; PBR; AD; BcTSPO; MS; PKA; IMM; fP; EP; PSP; OMM; MAB; PCA; TBAH; SUV; FTD; ROS; SUVR; CNS disorders; DLB; PRAX-1; SAH; PAP7; VT; RRMS; BMSC; CBD; MRI; SAR; ANT; CNS; Am; TLE; BP; CRAC; LPS; P2X7R; SA; SNL; PDD; d.c. RCYs; KA; MMSE; SNR; MSA; Microglial activation; Positron emission tomography (PET); HAB; Neuroinflammation; PpIX; p.i; MAO-B; LAB; n.d.c. RCYs; OCD; MCI; PD; VDAC; HD; PET; SCIDY; Am, molar activities; DLB, Lewy body dementias; RCYs, radiochemical yields; fP, plasma free fraction; MCI, mild cognitive impairment; SA, specific activity; PDD, PD dementia; SCIDY, spirocyclic iodonium ylide; SAR, structure–activity relationship; CRAC, cholesterol recognition amino acid consensus sequence; HSE, herpes simplex encephalitis; MAB, mixed-affinity binding; NAA/Cr, N-acetylaspartate/creatine; MMSE, mini-mental state examination; PAP7, RIa-associated protein; PBR, peripheral benzodiazepine receptor; SNL, selective neuronal loss; p.i., post-injection; HAB, high-affinity binding; OMM, outer mitochondrial membrane; PET, positron emission tomography; IMM, inner mitochondrial membrane; FTD, frontotemporal dementia; d.c. RCYs, decay-corrected radiochemical yields; MSA, multiple system atrophy; PD, Parkinson's disease; LAB, low-affinity binding; AD, Alzheimer's disease; TBI, traumatic brain injury; LPS, lipopolysaccharide; BPND, non-displaceable binding potential; BcTSPO, Bacillus cereus TSPO; PKA, protein kinase A; PpIX, protoporphyrin IX; KA, kainic acid; TSPO, translocator protein; VT, distribution volume; TBAH, tetrabutyl ammonium hydroxide; n.d.c. RCYs, non-decay-corrected radiochemical yields; TLE, temporal lobe epilepsy; P2X7R, purinergic receptor P2X7; ALS, amyotrophic lateral sclerosis; PRAX-1, PBR-associated protein 1; SUVR, standard uptake volume ratio; dMCAO, distal middle cerebral artery occlusion; BP, binding potential; VDAC, voltage-dependent anion channel; ANT, adenine nucleotide transporter; BMSC, bone marrow stromal cells; EP, epilepsy; ROS, reactive oxygen species; MDD, major depressive disorder; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; SUV, standard uptake volume; HD, Huntington's disease; QA, quinolinic acid; BBB, blood‒brain barrier; CBD, corticobasal degeneration; PCA, posterior cortical atrophy; MS, multiple sclerosis; MRI, magnetic resonance imaging; CNS, central nervous system; OCD, obsessive compulsive disorder; PSP, progressive supranuclear palsy; SAH, subarachnoid hemorrhage; MAO-B, monoamine oxidase B; SNR, signal to noise ratio; RRMS, relapsing remitting multiple sclerosis

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 c...