TY - JOUR
T1 - The impact of dopamine D2-like agonist/antagonist on [18F]VAT PET measurement of VAChT in the brain of nonhuman primates
AU - Liu, Hui
AU - Luo, Zonghua
AU - Gu, Jiwei
AU - Su, Yi
AU - Flores, Hubert
AU - Parsons, Stanley M.
AU - Zhou, Yun
AU - Perlmutter, Joel S.
AU - Tu, Zhude
N1 - Funding Information:
This work was supported by United States NIH grants NS061025 , NS075527 , MH092797 , and NS103988 . The authors thank John Hood, Emily Williams, and Darryl Craig for their assistance with the nonhuman primate microPET studies. The authors also thank Washington University Cyclotron Facility for [ 18 F]fluoride production.
Funding Information:
This work was supported by United States NIHgrants NS061025, NS075527, MH092797, and NS103988. The authors thank John Hood, Emily Williams, and Darryl Craig for their assistance with the nonhuman primate microPET studies. The authors also thank Washington University Cyclotron Facility for [18F]fluoride production.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2020/2/15
Y1 - 2020/2/15
N2 - Vesicular acetylcholine transporter (VAChT) is a promising target for a PET measure of cholinergic deficits which contribute to cognitive impairments. Dopamine D2-like agonists and antagonists are frequently used in the elderly and could alter cholinergic function and VAChT level. Therefore, pretreatment with dopamine D2-like drugs may interfere with PET measures using [18F]VAT, a specific VAChT radioligand. Herein, we investigated the impact of dopaminergic D2-like antagonist/agonist on VAChT level in the brain of macaques using [18F]VAT PET. PET imaging studies were carried out on macaques at baseline or pretreatment conditions. For pretreatment, animals were injected using a VAChT inhibitor (-)-vesamicol, a D2-like antagonist (-)-eticlopride, and a D2-like agonist (-)-quinpirole, separately. (-)-Vesamicol was injected at escalating doses of 0.025, 0.05, 0.125, 0.25 and 0.35 mg/kg; (-)-eticlopride was injected at escalating doses of 0.01, 0.10 and 0.30 mg/kg; (-)-quinpirole was injected at escalating doses of 0.20, 0.30, and 0.50 mg/kg. PET data showed [18F]VAT uptake declined in a dose-dependent manner by (-)-vesamicol pretreatment, demonstrating [18F]VAT uptake is sensitive to reflect the availability of VAChT binding sites. Furthermore, (-)-eticlopride increased [18F]VAT striatal uptake in a dose-dependent manner, while (-)-quinpirole decreased its uptake, suggesting striatal VAChT levels can be regulated by D2-like drug administration. Our findings confirmed [18F]VAT offers a reliable tool to in vivo assess the availability of VAChT binding sites. More importantly, PET with [18F]VAT successfully quantified the impact of dopaminergic D2-like drugs on striatal VAChT level, suggesting [18F]VAT has great potential for investigating the interaction between dopaminergic and cholinergic systems in vivo.
AB - Vesicular acetylcholine transporter (VAChT) is a promising target for a PET measure of cholinergic deficits which contribute to cognitive impairments. Dopamine D2-like agonists and antagonists are frequently used in the elderly and could alter cholinergic function and VAChT level. Therefore, pretreatment with dopamine D2-like drugs may interfere with PET measures using [18F]VAT, a specific VAChT radioligand. Herein, we investigated the impact of dopaminergic D2-like antagonist/agonist on VAChT level in the brain of macaques using [18F]VAT PET. PET imaging studies were carried out on macaques at baseline or pretreatment conditions. For pretreatment, animals were injected using a VAChT inhibitor (-)-vesamicol, a D2-like antagonist (-)-eticlopride, and a D2-like agonist (-)-quinpirole, separately. (-)-Vesamicol was injected at escalating doses of 0.025, 0.05, 0.125, 0.25 and 0.35 mg/kg; (-)-eticlopride was injected at escalating doses of 0.01, 0.10 and 0.30 mg/kg; (-)-quinpirole was injected at escalating doses of 0.20, 0.30, and 0.50 mg/kg. PET data showed [18F]VAT uptake declined in a dose-dependent manner by (-)-vesamicol pretreatment, demonstrating [18F]VAT uptake is sensitive to reflect the availability of VAChT binding sites. Furthermore, (-)-eticlopride increased [18F]VAT striatal uptake in a dose-dependent manner, while (-)-quinpirole decreased its uptake, suggesting striatal VAChT levels can be regulated by D2-like drug administration. Our findings confirmed [18F]VAT offers a reliable tool to in vivo assess the availability of VAChT binding sites. More importantly, PET with [18F]VAT successfully quantified the impact of dopaminergic D2-like drugs on striatal VAChT level, suggesting [18F]VAT has great potential for investigating the interaction between dopaminergic and cholinergic systems in vivo.
KW - Dopaminergic D-like drugs
KW - Nonhuman primates
KW - PET
KW - Vesicular acetylcholine transporter
KW - [F]VAT
UR - http://www.scopus.com/inward/record.url?scp=85075627827&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2019.105152
DO - 10.1016/j.ejps.2019.105152
M3 - Article
C2 - 31740395
AN - SCOPUS:85075627827
SN - 0928-0987
VL - 143
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
M1 - 105152
ER -