Design, Synthesis, and In Vitro and In Vivo Evaluation of an 18 F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer

Rosenberg, Adam J.; Liu, Hui; Jin, Hongjun; Yue, Xuyi; Riley, Sean; Brown, Steven J.; Tu, Zhude

doi:10.1021/acs.jmedchem.6b00390

Title: Design, Synthesis, and In Vitro and In Vivo Evaluation of an ¹⁸ F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P₁) PET Tracer

Journal Article · Thu Jun 09 00:00:00 EDT 2016 · Journal of Medicinal Chemistry

DOI:https://doi.org/10.1021/acs.jmedchem.6b00390· OSTI ID:1466768

Rosenberg, Adam J. ^[1]; Liu, Hui ^[1]; Jin, Hongjun ^[1]; Yue, Xuyi ^[1]; Riley, Sean ^[2]; Brown, Steven J. ^[2]; Tu, Zhude ^[1]

Washington University School of Medicine, St. Louis, MO (United States). Department of Radiology
The Scripps Research Institute Molecular Screening Center, La Jolla, CA (United States)

We present that sphingosine 1-phosphate receptor 1 (S1P₁) plays a pivotal signaling role in inflammatory response; because S1P₁ modulation has been identified as a therapeutic target for various diseases, a PET tracer for S1P₁ would be a useful tool. Fourteen fluorine-containing analogues of S1P ligands were synthesized and their in vitro binding potency measured; four had high potency and selectivity for S1P₁ (S1P₁ IC₅₀ < 10 nM, >100-fold selectivity for S1P₁ over S1P₂ and S1P₃). The most potent ligand, 28c (IC₅₀ = 2.63 nM for S1P₁) was ¹⁸F-labeled and evaluated in a mouse model of LPS-induced acute liver injury to determine its S1P₁-binding specificity. The results from biodistribution, autoradiography, and microPET imaging showed higher [¹⁸F]28c accumulation in the liver of LPS-treated mice than controls. Increased expression of S1P₁ in the LPS model was confirmed by immunohistochemical analysis (IHC). Finally, these data suggest that [¹⁸F]28c is a S1P₁ PET tracer with high potential for imaging S1P₁ in vivo.

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Research Organization:: Washington Univ., St. Louis, MO (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0008432; SC0012737

OSTI ID:: 1466768

Journal Information:: Journal of Medicinal Chemistry, Vol. 59, Issue 13; ISSN 0022-2623

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 20 works

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Title: Design, Synthesis, and In Vitro and In Vivo Evaluation of an ¹⁸ F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P₁) PET Tracer