Dataset Information

Development of ¹⁸F-Labeled Radiotracers for PET Imaging of the Adenosine A_2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation.

ABSTRACT: The adenosine A_2A receptor (A_2AR) 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 A_2AR-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; K_i(hA_2AR) = 5.3 nM) and the 2-fluorobenzyl derivate (PPY2; K_i(hA_2AR) = 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.

SUBMITTER: Lai TH

PROVIDER: S-EPMC7956753 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Development of 18F-Labeled Radiotracers for PET Imaging of the Adenosine A2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation.

Lai Thu Hang TH Schröder Susann S Toussaint Magali M Dukić-Stefanović Sladjana S Kranz Mathias M Ludwig Friedrich-Alexander FA Fischer Steffen S Steinbach Jörg J Deuther-Conrad Winnie W Brust Peter P Moldovan Rareş-Petru RP

International journal of molecular sciences 20210225 5

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</sub ...[more]

PMID: 33669003

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Dataset Information

Development of ¹⁸F-Labeled Radiotracers for PET Imaging of the Adenosine A_2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation.

Publications

Development of <sup>18</sup>F-Labeled Radiotracers for PET Imaging of the Adenosine A<sub>2A</sub> Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation.

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