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Translation of 11C-labeled tracer synthesis to a CGMP environment as exemplified by [11C]ER176 for PET imaging of human TSPO

Nature Protocols volume 16, pages 4419–4445 (2021)Cite this article

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Abstract

Radiotracers labeled with carbon-11 (t1/2 = 20.4 min) are widely used with positron emission tomography for biomedical research. Radiotracers must be produced for positron emission tomography studies in humans according to prescribed time schedules while also meeting current good manufacturing practice. Translation of an experimental radiosynthesis to a current good manufacturing practice environment is challenging. Here we exemplify such translation with a protocol for the production of an emerging radiotracer for imaging brain translocator protein 18 kDa, namely [11C]ER176. This radiotracer is produced by rapid conversion of cyclotron-produced [11C]carbon dioxide into [11C]iodomethane, which is then used to treat N-desmethyl-ER176 in the presence of base (tBuOK) at room temperature for 5 min. [11C]ER176 is separated in high purity by reversed-phase HPLC and formulated for intravenous injection in sterile ethanol–saline. The radiosynthesis is reliable and takes 50 min. Quality control takes another 20 min. All aspects of the protocol, including quality control, are discussed.

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Fig. 1: Labeling of the tertiary amido group in (R)-PK11195 and ER176 with carbon-11.
Fig. 2: Comparison of the method for producing [11C]ER176 in the laboratory for preclinical studies with that in a CGMP environment for clinical studies.
Fig. 3: A typical radiochromatogram obtained for the HPLC separation of [11C]ER176 from the reaction mixture.
Fig. 4: A typical chromatogram from the QC HPLC analysis of formulated [11C]ER176.
Fig. 5: Configuration of apparatus within the hot cell.
Fig. 6

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Data availability

Data in this protocol are from the cited literature. Any new data are provided as original source data in the Supplementary Information.

Code availability

Software are deposited at https://github.com/jinsoohong-netizen/ER176

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Acknowledgements

This work was supported by the Intramural Research Program of the National Institutes of Health (National Institute of Mental Health project number ZIA-MH002793). The authors are grateful to the NIH Clinical Center PET Department (Chief: P. Herscovitch) for cyclotron production of carbon-11. The authors thank S. Lu (NIMH) for careful checking of the manuscript.

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Authors and Affiliations

  1. Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    Jinsoo Hong, Sanjay Telu, Yi Zhang, William H. Miller, H. Umesha Shetty, Cheryl L. Morse & Victor W. Pike

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Contributions

V.W.P. conceived and supervised the project. Y.Z, S.T. and C.L.M. developed the radiochemistry. J.H. developed the automated radiosynthesis procedure and analytical methods. S.T., C.L.M., W.H.M. and J.H. performed productions and analyses. H.U.S. performed mass spectrometry. All authors analyzed the data, and read and approved the manuscript.

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Correspondence to Victor W. Pike.

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Fujita, M. et al. EJNMMI Res. 7, 84 (2017): https://ejnmmires.springeropen.com/track/pdf/10.1186/s13550-017-0334-8.pdf

Extended data

Extended Data Fig. 1

Overall setup of the [11C]ER176 production apparatus.

Supplementary information

Supplementary Information

Supplementary Methods 1–9, Supplementary Figs. 1–8 and Supplementary Tables 1–6.

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Hong, J., Telu, S., Zhang, Y. et al. Translation of 11C-labeled tracer synthesis to a CGMP environment as exemplified by [11C]ER176 for PET imaging of human TSPO. Nat Protoc 16, 4419–4445 (2021). https://doi.org/10.1038/s41596-021-00584-4

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