TY - JOUR
T1 - Evaluation of the novel TSPO radiotracer 2-(7-butyl-2-(4-(2-([18F]fluoroethoxy)phenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide in a preclinical model of neuroinflammation
AU - Tang, Dewei
AU - Fujinaga, Masayuki
AU - Hatori, Akiko
AU - Zhang, Yiding
AU - Yamasaki, Tomoteru
AU - Xie, Lin
AU - Mori, Wakana
AU - Kumata, Katsushi
AU - Liu, Jianjun
AU - Manning, H. Charles
AU - Huang, Gang
AU - Zhang, Ming Rong
N1 - Funding Information:
We would like to thank the staff at the National Institute of Radiological Sciences for their support with the cyclotron operation, radioisotope production, radiosynthesis, and animal experiments. The study was also partly supported by research grants from The National Science Foundation of China (Grant No. 81530053 , 81471685 and 81601536 ). Appendix A
Funding Information:
We would like to thank the staff at the National Institute of Radiological Sciences for their support with the cyclotron operation, radioisotope production, radiosynthesis, and animal experiments. The study was also partly supported by research grants from The National Science Foundation of China (Grant No. 81530053, 81471685 and 81601536).
Publisher Copyright:
© 2018
PY - 2018/4/25
Y1 - 2018/4/25
N2 - Translocator Protein (18 kDa, TSPO) is regarded as a useful biomarker for neuroinflammation imaging. TSPO PET imaging could be used to understand the role of neuroinflammation in brain diseases and as a tool for evaluating novel therapeutic effects. As a promising TSPO probe, [18F]DPA-714 is highly specific and offers reliable quantification of TSPO in vivo. In this study, we further radiosynthesized and evaluated another novel TSPO probe, 2-(7-butyl-2-(4-(2-[18F]fluoroethoxy)phenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([18F]VUIIS1018A), which features a 700-fold higher binding affinity for TSPO than that of [18F]DPA-714. We evaluated the performance of [18F]VUIIS1018A using dynamic in vivo PET imaging, radiometabolite analysis, in vitro autoradiography assays, biodistribution analysis, and blocking assays. In vivo study using this probe demonstrated high signal-to-noise ratio, binding potential (BPND), and binding specificity in preclinical neuroinflammation studies. Taken together, these findings indicate that [18F]VUIIS1018A may serve as a novel TSPO PET probe for neuroinflammation imaging.
AB - Translocator Protein (18 kDa, TSPO) is regarded as a useful biomarker for neuroinflammation imaging. TSPO PET imaging could be used to understand the role of neuroinflammation in brain diseases and as a tool for evaluating novel therapeutic effects. As a promising TSPO probe, [18F]DPA-714 is highly specific and offers reliable quantification of TSPO in vivo. In this study, we further radiosynthesized and evaluated another novel TSPO probe, 2-(7-butyl-2-(4-(2-[18F]fluoroethoxy)phenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([18F]VUIIS1018A), which features a 700-fold higher binding affinity for TSPO than that of [18F]DPA-714. We evaluated the performance of [18F]VUIIS1018A using dynamic in vivo PET imaging, radiometabolite analysis, in vitro autoradiography assays, biodistribution analysis, and blocking assays. In vivo study using this probe demonstrated high signal-to-noise ratio, binding potential (BPND), and binding specificity in preclinical neuroinflammation studies. Taken together, these findings indicate that [18F]VUIIS1018A may serve as a novel TSPO PET probe for neuroinflammation imaging.
KW - Neuroinflammation
KW - Positron Emission Tomography (PET)
KW - TSPO
KW - [F]DPA-714
KW - [F]VUIIS1018A
UR - http://www.scopus.com/inward/record.url?scp=85042637362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042637362&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2018.02.076
DO - 10.1016/j.ejmech.2018.02.076
M3 - Article
C2 - 29505933
AN - SCOPUS:85042637362
SN - 0223-5234
VL - 150
SP - 1
EP - 8
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -