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Development of 18F-labeled radiotracers for PET imaging of the adenosine A2A receptor: Synthesis, radiolabeling and preliminary biological evaluation

Authors :
(0000-0001-8157-8979) Lai, T. H.
(0000-0001-6440-1362) Schröder, S.
(0000-0002-1136-3857) Toussaint, M.
Dukic-Stefanovic, S.
Kranz, M.
(0000-0002-4358-5171) Ludwig, F.-A.
Fischer, S.
Steinbach, J.
(0000-0003-3168-3062) Deuther-Conrad, W.
(0000-0001-5555-7058) Brust, P.
(0000-0003-3119-7945) Moldovan, R.-P.
(0000-0001-8157-8979) Lai, T. H.
(0000-0001-6440-1362) Schröder, S.
(0000-0002-1136-3857) Toussaint, M.
Dukic-Stefanovic, S.
Kranz, M.
(0000-0002-4358-5171) Ludwig, F.-A.
Fischer, S.
Steinbach, J.
(0000-0003-3168-3062) Deuther-Conrad, W.
(0000-0001-5555-7058) Brust, P.
(0000-0003-3119-7945) Moldovan, R.-P.
Source :
International Journal of Molecular Sciences 22(2021)5, 2285
Publication Year :
2021

Abstract

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. 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.

Details

Database :
OAIster
Journal :
International Journal of Molecular Sciences 22(2021)5, 2285
Notes :
application/pdf, German
Publication Type :
Electronic Resource
Accession number :
edsoai.on1415626617
Document Type :
Electronic Resource