Development of 18F-Labeled Radiotracers for PET Imaging of the Adenosine A2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation.
Thu Hang LaiSusann SchröderMagali ToussaintSladjana Dukić-StefanovićMathias KranzFriedrich-Alexander LudwigSteffen FischerJörg SteinbachWinnie Deuther-ConradPeter BrustRareş-Petru MoldovanPublished in: International journal of molecular sciences (2021)
The adenosine A2A receptor (A2AR) represents a potential therapeutic target for neurodegenerative diseases. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor changes of receptor density and/or occupancy during the A2AR-tailored therapy, we designed a library of fluorinated analogs based on a recently published lead compound (PPY). Among those, the highly affine 4-fluorobenzyl derivate (PPY1; Ki(hA2AR) = 5.3 nM) and the 2-fluorobenzyl derivate (PPY2; Ki(hA2AR) = 2.1 nM) were chosen for 18F-labeling via an alcohol-enhanced copper-mediated procedure starting from the corresponding boronic acid pinacol ester precursors. Investigations of the metabolic stability of [18F]PPY1 and [18F]PPY2 in CD-1 mice by radio-HPLC analysis revealed parent fractions of more than 76% of total activity in the brain. Specific binding of [18F]PPY2 on mice brain slices was demonstrated by in vitro autoradiography. In vivo PET/magnetic resonance imaging (MRI) studies in CD-1 mice revealed a reasonable high initial brain uptake for both radiotracers, followed by a fast clearance.
Keyphrases
- pet imaging
- positron emission tomography
- computed tomography
- magnetic resonance imaging
- high fat diet induced
- resting state
- white matter
- pet ct
- contrast enhanced
- cerebral ischemia
- photodynamic therapy
- single cell
- functional connectivity
- radiation therapy
- binding protein
- wild type
- magnetic resonance
- mass spectrometry
- protein kinase
- minimally invasive
- insulin resistance
- multiple sclerosis
- bone marrow
- risk assessment
- metabolic syndrome
- human health
- high performance liquid chromatography
- smoking cessation
- locally advanced
- nk cells