PET Imaging of the Adenosine A2A Receptor in the Rotenone-Based Mouse Model of Parkinson's Disease with [18F]FESCH Synthesized by a Simplified Two-Step One-Pot Radiolabeling Strategy

被引：13
作者：
Schroeder, Susann [1 ]
Thu Hang Lai [2 ]
Toussaint, Magali [2 ]
Kranz, Mathias [3 ,4 ]
Chovsepian, Alexandra [5 ]
Shang, Qi [6 ,7 ]
Dukic-Stefanovic, Sladjana [2 ]
Deuther-Conrad, Winnie [2 ]
Teodoro, Rodrigo [2 ]
Wenzel, Barbara [2 ]
Moldovan, Rares-Petru [2 ]
Pan-Montojo, Francisco [5 ,6 ]
Brust, Peter [2 ]
机构：
[1] ROTOP Pharmaka Ltd, Dept Res & Dev, D-01328 Dresden, Germany
[2] HZDR, Dept Neuroradiopharmaceut, Inst Radiopharmaceut Canc Res, Res Site Leipzig, D-04318 Leipzig, Germany
[3] Univ Hosp North Norway UNN, PET Imaging Ctr, N-9009 Tromso, Norway
[4] Arctic Univ Norway, Nucl Med & Radiat Biol Res Grp, N-9009 Tromso, Norway
[5] Ludwig Maximilians Univ LMU Munich, Dept Psychiat, Univ Hosp Munich, D-80336 Munich, Germany
[6] Ludwig Maximilians Univ LMU Munich, Dept Neurol, Univ Hosp Munich, D-81377 Munich, Germany
[7] TUD, Clin Neurol, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany
来源：
MOLECULES | 2020年 / 25卷 / 07期
关键词：
adenosine A(2A) receptor; Parkinson's disease; rotenone-based mouse model; PET imaging; F-18]FESCH; two-step one-pot radiosynthesis; IN-VIVO EVALUATION; GLIAL METABOLISM; DOUBLE-BLIND; BRAIN; ACETATE; RAT; FLUOROACETATE; RADIOLIGAND; RADIOTRACER; ANTAGONISTS;
D O I：
10.3390/molecules25071633
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The adenosine A(2A) receptor (A(2A)R) is regarded as a particularly appropriate target for non-dopaminergic treatment of Parkinson's disease (PD). An increased A(2A)R availability has been found in the human striatum at early stages of PD and in patients with PD and dyskinesias. The aim of this small animal positron emission tomography/magnetic resonance (PET/MR) imaging study was to investigate whether rotenone-treated mice reflect the aspect of striatal A(2A)R upregulation in PD. For that purpose, we selected the known A(2A)R-specific radiotracer [F-18]FESCH and developed a simplified two-step one-pot radiosynthesis. PET images showed a high uptake of [F-18]FESCH in the mouse striatum. Concomitantly, metabolism studies with [F-18]FESCH revealed the presence of a brain-penetrant radiometabolite. In rotenone-treated mice, a slightly higher striatal A(2A)R binding of [F-18]FESCH was found. Nonetheless, the correlation between the increased A(2A)R levels within the proposed PD animal model remains to be further investigated.
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页数：15
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