In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18kDa (TSPO) in monkey brain DOI Creative Commons
Xuefeng Yan, Fabrice G. Siméon, Jeih‐San Liow

et al.

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 24, 2022

Abstract Purpose : 18 F-SF51 was previously found to have high binding affinity and selectivity for 18kDa translocator protein (TSPO) in mouse brain. This study sought further evaluate the suitability of absolute quantification TSPO monkey Methods: Positron emission tomography (PET) imaging performed brain (n=3) at baseline after pre-blockade with ligands PK11195 PBR28. calculated as total distribution volume corrected free parent fraction plasma ( V T / f P ) using a two-tissue compartment model. Receptor occupancy nondisplaceable uptake were determined via Lassen plot. Binding potential BP ND ratio specific uptake. Time stability used an indirect probe detect radiometabolite accumulation In vivo ex experiments mice determine radioligand. Results: After injection, concentration radioactivity peaked 2.0 standardized value (SUV) ~10 minutes declined 30% peak 180 minutes. generally (203±15 mL· cm -3 decreased by ~90% blockade PK11195. whole 7.6 ± 4.3. values reached levels similar terminal 180-minute 70 remained relatively stable thereafter excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated Ex showed 96% parent. No observed skull, lack defluorination vivo. Conclusion: The results demonstrate is radioligand good well time receptor binding. Collectively, suggest warrants evaluation humans.

Language: Английский

Current status of PET tracers for the early diagnosis of Alzheimer's disease DOI
Yuying Li, Tianqing Liu, Qi Zeng

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 172, P. 117546 - 117546

Published: Jan. 17, 2024

Language: Английский

Citations

5
Structure-based drug design for TSPO: Challenges and opportunities DOI Creative Commons

M. Giladi,

Andrew P. Montgomery, Michael Kassiou

et al.

Biochimie, Journal Year: 2024, Volume and Issue: 224, P. 41 - 50

Published: Sept. 1, 2024

The translocator protein 18 kDa (TSPO) is an evolutionarily conserved mitochondrial transmembrane implicated in various neuropathologies and inflammatory conditions, making it a longstanding diagnostic therapeutic target of interest. Despite the development classes TSPO ligand chemotypes, elucidation bacterial non-human mammalian experimental structures, many unknowns exist surrounding its differential structural functional features health disease. There are several limitations associated with currently used computational methodologies for modelling native structure ligand-binding behaviour this enigmatic protein. In perspective, we provide critical analysis developments uses these methods, outlining their uses, inherent limitations, continuing challenges. We offer suggestions unexplored opportunities that use which promise enhancing our understanding TSPO.

Language: Английский

Citations

3
Synthesis and evaluation of TSPO-targeting radioligand [18F]F-TFQC for PET neuroimaging in epileptic rats DOI Creative Commons
Wenhui Fu, Qingyu Lin,

Zhequan Fu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 15(2), P. 722 - 736

Published: June 3, 2024

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of TSPO-targeting radioligand [18F]F-TFQC, an m-trifluoromethyl ER176 analog, in PET neuroimaging epileptic rats. Initially, [18F]F-TFQC was synthesized a radiochemical yield 8%–10% (EOS), purity over 99%, specific activity 38.21 ± 1.73 MBq/nmol (EOS). After determining that exhibited good biochemical properties, performed rats at multiple time points various stages disease progression. imaging showed uptake right hippocampus (KA-injected site, i.e., epileptogenic zone), which most pronounced 1 week (T/NT 1.63 0.21) month 1.66 0.20). results were further validated using autoradiography pathological analysis. Thus, reflect TSPO levels localize zone, thereby offering potential for monitoring guiding anti-inflammatory treatment patients

Language: Английский

Citations

3
Preclinical Evaluation of Novel PET Probes for Dementia DOI
Romy Cools, Kobe Kerkhofs, Renan C.F. Leitao

et al.

Seminars in Nuclear Medicine, Journal Year: 2023, Volume and Issue: 53(5), P. 599 - 629

Published: May 5, 2023

Language: Английский

Citations

7
In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18 kDa (TSPO) in monkey brain DOI Creative Commons
Xuefeng Yan, Fabrice G. Siméon, Jeih‐San Liow

et al.

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2023, Volume and Issue: 50(10), P. 2962 - 2970

Published: May 30, 2023

[

Citations

6
Radiotracers for Imaging of Inflammatory Biomarkers TSPO and COX-2 in the Brain and in the Periphery DOI Open Access

Bright Chukwunwike Uzuegbunam,

Christoph Rummel,

Damiano Librizzi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17419 - 17419

Published: Dec. 13, 2023

Inflammation involves the activation of innate immune cells and is believed to play an important role in development progression both infectious non-infectious diseases such as neurodegeneration, autoimmune diseases, pulmonary cancer. brain marked by upregulation translocator protein (TSPO) microglia. High TSPO levels are also found, for example, macrophages cases rheumatoid arthritis malignant tumor compared their relatively low physiological expression. The same applies cyclooxgenase-2 (COX-2), which constitutively expressed kidney, brain, thymus gastrointestinal tract, but induced microglia, synoviocytes during inflammation. This puts COX-2 spotlight targets diagnosis Imaging modalities, positron emission tomography single-photon tomography, can be used localize inflammatory processes track over time. They could enable monitoring efficacy therapy predict its outcome. review focuses on current PET SPECT tracers, not only detection neuroinflammation, emerging diagnostic measures other rheumatic arthritis, cancer, cardiac inflammation lung diseases.

Language: Английский

Citations

6
Evaluation of damage discrimination in dopaminergic neurons using dopamine transporter PET tracer [18F]FECNT-d4 DOI Creative Commons

Jie Tang,

Congjin Liu,

Chunyi Liu

et al.

EJNMMI Research, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 29, 2024

Parkinson's disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[

Language: Английский

Citations

0
Evaluation of Damage Discrimination in Dopaminergic Neurons Using Dopamine Transporter PET Tracer [18F]FECNT-d4 DOI

Jie Tang,

Congjin Liu,

Chunyi Liu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 2, 2024

Abstract Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands， positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl) nortropane ([18F]FECNT) been utilized as PET tracer image dopamine transporter (DAT) integrity striatal presynaptic dopaminergic terminals. However, presence brain-penetrant metabolites produced by [18F]FECNT may impact accuracy imaging. In previous research, we developed 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl-1,1,2,2-d4) ([18F]FECNT-d4), deuterated derivative enhanced stability plasma striatum, along slower washout rate. this study, further investigated potential [18F]FECNT-d4 detect neuron degeneration disease. This involved unilaterally-lesioned model rats in vitro autoradiography conducted postmortem brain sections. Results: images revealed reduced uptake ipsilateral striatum stereotactically injected 6-hydroxydopamine hydrochloride (6-OHDA). Compared sham group, ratio standardized value (SUV) contralateral decreased 13%, 23%, 63% mild, moderate, severe lesioned groups, respectively. Dopaminergic denervation observed was supported behavioral assessments, immunostaining, monoamine concentration tests. Moreover, microPET results exhibited positive correlations measurements, except for apomorphine-induced rotational behavior test, which showed negative correlation. Additionally, approximately 40% lower sections patient compared healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below current Food Drug Administration limit radiation exposure. Conclusion: Our findings demonstrate that accurately estimates levels 6-OHDA-induced effectively distinguishes between patients individuals. highly sensitive safe probe holds promising application diagnosis monitoring

Language: Английский

Citations

0
Design of a deuterated TSPO tracer and its application in glioma and atherosclerotic imaging DOI
Yong Huang,

Zeng Jiang,

Lu Zhang

et al.

New Journal of Chemistry, Journal Year: 2024, Volume and Issue: 49(3), P. 1100 - 1109

Published: Dec. 11, 2024

TSPO tracer [ 18 F]BIBD-239-d2 is designed and applied to improve imaging of glioma atherosclerosis.

Language: Английский

Citations

0
In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18kDa (TSPO) in monkey brain DOI Creative Commons
Xuefeng Yan, Fabrice G. Siméon, Jeih‐San Liow

et al.

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 24, 2022

Abstract Purpose : 18 F-SF51 was previously found to have high binding affinity and selectivity for 18kDa translocator protein (TSPO) in mouse brain. This study sought further evaluate the suitability of absolute quantification TSPO monkey Methods: Positron emission tomography (PET) imaging performed brain (n=3) at baseline after pre-blockade with ligands PK11195 PBR28. calculated as total distribution volume corrected free parent fraction plasma ( V T / f P ) using a two-tissue compartment model. Receptor occupancy nondisplaceable uptake were determined via Lassen plot. Binding potential BP ND ratio specific uptake. Time stability used an indirect probe detect radiometabolite accumulation In vivo ex experiments mice determine radioligand. Results: After injection, concentration radioactivity peaked 2.0 standardized value (SUV) ~10 minutes declined 30% peak 180 minutes. generally (203±15 mL· cm -3 decreased by ~90% blockade PK11195. whole 7.6 ± 4.3. values reached levels similar terminal 180-minute 70 remained relatively stable thereafter excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated Ex showed 96% parent. No observed skull, lack defluorination vivo. Conclusion: The results demonstrate is radioligand good well time receptor binding. Collectively, suggest warrants evaluation humans.

Language: Английский

Citations

0