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Fully Automated Production of 11C-Doxepin for PET Imaging Histamine H1 Receptor

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Abstract

Objectives

11C-Doxepin is an established positron emission tomography (PET) probe for imaging the histamine H1 receptor, which is associated with various neurological disorders and allergic diseases. A fully automated current Good Manufacturing Practices (cGMP)-compliant radiosynthesis is therefore desirable in order to facilitate clinical PET studies. We report here a fully automated production method for 11C-doxepin using a multipurpose PET module for clinical use.

Methods

11C-Doxepin was radiosynthesized by N-[11C]methylation of nordoxepin using [11C]methyl iodide in DMF solvent, and then purified by HPLC, and finally reformulated with solid phase extraction (SPE) using a cGMP-compliant automated multipurpose PET module developed in house. The final product was analyzed and subjected to quality control according to current US Pharmacopeia requirements.

Results

The radiochemical yield (decay corrected) of 11C-doxepin for clinical use was 47.0 ± 5.2% (n = 12) based on [11C]methyl iodide, moreover the radiochemical purity of 11C-doxepin was more than 97.5% with 1,200 ± 500 Ci/mmol specific activity(end of production). The total production time of 11C-doxepin was 37 min from end of bombardment (EOB) with the final product passing all tests under cGMP requirements for clinical use.

Conclusions

A simplified and reliable fully automated production of 11 C-doxepin for clinical use was developed, allowing the synthesis of the tracer with high yield using a cGMP-compliant module and procedure. The success of this approach could make the PET tracer 11 C-doxepin more accessible for clinical studies.

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Acknowledgements

We would like to thank the staff members of the Children's Hospital of Michigan PET center for their service and support.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. PET Center, Children’s Hospital of Michigan/Detroit Medical Center, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA

    Hancheng Cai, Thomas J. Mangner, Otto Muzik, Xin Lu, Pulak K. Chakraborty, Diane C. Chugani & Harry T. Chugani

  2. Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA

    Hancheng Cai, Otto Muzik, Xin Lu, Diane C. Chugani & Harry T. Chugani

  3. Department of Radiology, Wayne State University School of Medicine, Detroit, MI, USA

    Hancheng Cai, Thomas J. Mangner, Otto Muzik, Pulak K. Chakraborty, Diane C. Chugani & Harry T. Chugani

  4. Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA

    Otto Muzik & Harry T. Chugani

Authors
  1. Hancheng Cai
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  2. Thomas J. Mangner
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  3. Otto Muzik
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  4. Xin Lu
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  5. Pulak K. Chakraborty
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  6. Diane C. Chugani
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  7. Harry T. Chugani
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Correspondence to Hancheng Cai.

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Cai, H., Mangner, T.J., Muzik, O. et al. Fully Automated Production of 11C-Doxepin for PET Imaging Histamine H1 Receptor. Mol Imaging Biol 14, 546–552 (2012). https://doi.org/10.1007/s11307-011-0535-x

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  • DOI: https://doi.org/10.1007/s11307-011-0535-x

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