Optimization and synthesis of an 18F-labeled dopamine D3 receptor ligand using [18F]fluorophenylazocarboxylic tert-butylester

Nebel N, Maschauer S, Hocke C, Hübner H, Gmeiner P, Prante O (2016)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2016

Journal

Book Volume: 59

Pages Range: 48-53

Journal Issue: 2

DOI: 10.1002/jlcr.3361

Abstract

There is still no efficient fluorine-18-labeled dopamine D subtype selective receptor ligand for studies with positron emission tomography. We aim at improving the D selectivity and hydrophilicity of a candidate ligand by changing the substitution pattern to a 2,3-dichlorophenylpiperazine and hydroxylation of the butyl chain. The compound [F]3 exhibited D affinity of K = 3.6 nM, increased subtype selectivity (K(D/D) = 60), and low affinity to 5-HT and α receptors (K (5-HT/D) = 34; K (α/D) = 100). The two-step radiosynthesis was optimized for analog [F]4 by reducing the necessary concentration of the precursor amine (57 mM), which reacted with [F]fluorophenylazocarboxylic tert-butylester under basic conditions. The optimization of the base (Cs CO, 23 mM) and the adjustment of reaction temperature led to the radiochemical yield of 63% after 5 min at 35C. The optimized reaction conditions were transferred on to the synthesis of [F]3 with an overall non-decay corrected yield of 8-12% in a specific activity of 32-102 GBq/μmol after a total synthesis time of 30-35 min. This provides a D radioligand candidate with improved attributes concerning selectivity and radiosynthesis for further preclinical studies.

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APA:

Nebel, N., Maschauer, S., Hocke, C., Hübner, H., Gmeiner, P., & Prante, O. (2016). Optimization and synthesis of an 18F-labeled dopamine D3 receptor ligand using [18F]fluorophenylazocarboxylic tert-butylester. Journal of Labelled Compounds and Radiopharmaceuticals, 59(2), 48-53. https://dx.doi.org/10.1002/jlcr.3361

MLA:

Nebel, Natascha, et al. "Optimization and synthesis of an 18F-labeled dopamine D3 receptor ligand using [18F]fluorophenylazocarboxylic tert-butylester." Journal of Labelled Compounds and Radiopharmaceuticals 59.2 (2016): 48-53.

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