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In vivo Characterization of Four 18F-Labeled S1PR1 Tracers for Neuroinflammation

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Abstract

Purpose

The sphingosine-1-phosphate receptor 1 (S1PR1) is an important biomarker for imaging inflammation in the central nervous system (CNS). Herein, we report our recent evaluation of four 18F-labeled S1PR1 tracers (18F-TZ43113, 18F-TZ35104, 18F-TZ4877, and 18F-TZ4881) in a rat model of multiple sclerosis (MS).

Procedures

MicroPET studies of each tracer’s uptake and kinetics were performed in an experimental autoimmune encephalomyelitis (EAE) rat model of MS to quantify upregulated S1PR1 expression in the lumbar spinal cord of EAE rats. Western blot analysis was conducted to confirm the differences in the expression of S1PR1 protein level between EAE and sham rats. Radiometabolite analysis was performed for the most promising candidate in rats.

Results

All four S1PR1 tracers detected increased S1PR1 levels in response to neuroinflammation in the lumbar spinal cord of EAE rats, which was supported by western blot results. The ranked order of tracer uptake in rat spinal cord was 18F-TZ4877 > 18F-TZ4881 > 18F-TZ35104 > 18F-TZ43113. 18F-TZ4877 had the highest uptake of the four tracers and showed good kinetic modeling fits in rat spinal cord using an image-based method of arterial blood input function. Radiometabolite analysis of 18F-TZ4877 showed good in vivo stability with no major radiometabolite accumulation in the rat brain.

Conclusion

Among these four new PET tracers, 18F-TZ4877 showed the most favorable profile for assessing S1PR1 expression in the EAE rat model of MS. Further characterization of these radiotracers in other models of neuroinflammation is warranted to identify a promising 18F-labeled tracer for imaging S1PR1 in vivo.

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Acknowledgments

The 18F-fluorine used this study was provided by Washington University Cyclotron Facility. The animal studies were conducted in Washington University Preclinical Imaging Facility. The authors would like to thank the staff of the Cyclotron Facility and the Preclinical Imaging Facility. The authors also thank Lynne Jones for manuscript editing.

Funding

This work was supported by the USA National Institutes of Health (NS075527, NS103957, NS103988, and EB025815).

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Authors and Affiliations

  1. Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., St. Louis, MO, 63110, USA

    Hui Liu, Zonghua Luo, Jiwei Gu, Hao Jiang, Sumit Joshi, Kooresh I. Shoghi, Yun Zhou, Robert J. Gropler, Tammie L. S. Benzinger & Zhude Tu

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  1. Hui Liu
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  2. Zonghua Luo
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  3. Jiwei Gu
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  4. Hao Jiang
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  7. Yun Zhou
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  10. Zhude Tu
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Correspondence to Zhude Tu.

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Liu, H., Luo, Z., Gu, J. et al. In vivo Characterization of Four 18F-Labeled S1PR1 Tracers for Neuroinflammation. Mol Imaging Biol 22, 1362–1369 (2020). https://doi.org/10.1007/s11307-020-01514-8

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