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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 7; p. 1633
• Main Authors: Schröder, Susann, Lai, Thu Hang, Toussaint, Magali, Kranz, Mathias, Chovsepian, Alexandra, Shang, Qi, Dukić-Stefanović, Sladjana, Deuther-Conrad, Winnie, Teodoro, Rodrigo, Wenzel, Barbara, Moldovan, Rareş-Petru, Pan-Montojo, Francisco, Brust, Peter
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 2020; MDPI
• Subjects: [18F]FESCH; Adenosine; adenosine A2A receptor; Dopamine; Dyskinesia; Labeling; Medisinske Fag: 700; Parkinson's disease; PET imaging; Phenols; rotenone-based mouse model; Studies; two-step one-pot radiosynthesis; VDP
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25071633

The adenosine A2A receptor (A2AR) is regarded as a particularly appropriate target for non-dopaminergic treatment of Parkinson’s disease (PD). An increased A2AR 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 A2AR upregulation in PD. For that purpose, we selected the known A2AR-specific radiotracer [18F]FESCH and developed a simplified two-step one-pot radiosynthesis. PET images showed a high uptake of [18F]FESCH in the mouse striatum. Concomitantly, metabolism studies with [18F]FESCH revealed the presence of a brain-penetrant radiometabolite. In rotenone-treated mice, a slightly higher striatal A2AR binding of [18F]FESCH was found. Nonetheless, the correlation between the increased A2AR levels within the proposed PD animal model remains to be further investigated.