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18F‐Labeled benzylpiperazine derivatives as highly selective ligands for imaging σ1 receptor with positron emission tomography.
- Source :
- Journal of Labelled Compounds & Radiopharmaceuticals; 6/30/2019, Vol. 62 Issue 8, p425-437, 13p
- Publication Year :
- 2019
-
Abstract
- We report the design, synthesis, and evaluation of a new series of benzylpiperazine derivatives as selective σ1 receptor ligands. All seven ligands possessed low nanomolar affinity for σ1 receptors (Ki(σ1) = 0.31‐4.19 nM) and high subtype selectivity (Ki(σ2)/Ki(σ1) = 50‐2448). The fluoroethoxy analogues also exhibited high selectivity toward the vesicular acetylcholine transporter (Ki(VAChT)/Ki(σ1) = 99‐18252). The corresponding radiotracers [18F]13, [18F]14, and [18F]16 with high selectivity (Ki(σ2)/Ki(σ1) > 100, Ki(VAChT)/Ki(σ1) > 1000) were prepared in 42% to 55% radiochemical yields (corrected for decay), greater than 99% radiochemical purity (RCP), and molar activity of about 120 GBq/μmol at the end of synthesis (EOS). All three radiotracers showed high initial brain uptake in mouse (8.37‐11.48% ID/g at 2 min), which was not affected by pretreatment with cyclosporine A, suggesting that they are not substrates for permeability‐glycoprotein (P‐gp). Pretreatment with SA4503 or haloperidol resulted in significantly reduced brain uptake (35%‐62% decrease at 30 min). In particular, [18F]16 displayed high brain‐to‐blood ratios and high invivo metabolic stability. Although it may not be an optimal neuroimaging agent because of its slow kinetics in the mouse brain, [18F]16 can serve as a lead compound for further structural modifications to explore new potential radiotracers for σ1 receptors. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03624803
- Volume :
- 62
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Journal of Labelled Compounds & Radiopharmaceuticals
- Publication Type :
- Academic Journal
- Accession number :
- 137437870
- Full Text :
- https://doi.org/10.1002/jlcr.3738