Fully automated production of 11C-doxepin for PET imaging histamine H1 receptor

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 11C-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 11C-doxepin more accessible for clinical studies.

Original languageEnglish (US)
Pages (from-to)546-552
Number of pages7
JournalMolecular Imaging and Biology
Volume14
Issue number5
DOIs
StatePublished - Oct 2012

Fingerprint

Doxepin
Histamine H1 Receptors
Positron-Emission Tomography
Pharmacopoeias
Solid Phase Extraction
Nervous System Diseases
Quality Control
Methylation
High Pressure Liquid Chromatography

Keywords

  • C-11 labeling
  • Doxepin
  • Histamine H1 receptor
  • PET
  • Radiosynthesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Cai, H., Mangner, T. J., Muzik, O., Lu, X., Chakraborty, P. K., Chugani, D. C., & Chugani, H. T. (2012). Fully automated production of 11C-doxepin for PET imaging histamine H1 receptor. Molecular Imaging and Biology, 14(5), 546-552. https://doi.org/10.1007/s11307-011-0535-x

Fully automated production of 11C-doxepin for PET imaging histamine H1 receptor. / Cai, Hancheng; Mangner, Thomas J.; Muzik, Otto; Lu, Xin; Chakraborty, Pulak K.; Chugani, Diane C.; Chugani, Harry T.

In: Molecular Imaging and Biology, Vol. 14, No. 5, 10.2012, p. 546-552.

Research output: Contribution to journalArticle

Cai, H, Mangner, TJ, Muzik, O, Lu, X, Chakraborty, PK, Chugani, DC & Chugani, HT 2012, 'Fully automated production of 11C-doxepin for PET imaging histamine H1 receptor', Molecular Imaging and Biology, vol. 14, no. 5, pp. 546-552. https://doi.org/10.1007/s11307-011-0535-x
Cai, Hancheng ; Mangner, Thomas J. ; Muzik, Otto ; Lu, Xin ; Chakraborty, Pulak K. ; Chugani, Diane C. ; Chugani, Harry T. / Fully automated production of 11C-doxepin for PET imaging histamine H1 receptor. In: Molecular Imaging and Biology. 2012 ; Vol. 14, No. 5. pp. 546-552.
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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 11C-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 11C-doxepin more accessible for clinical studies.",
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AU - Cai, Hancheng

AU - Mangner, Thomas J.

AU - Muzik, Otto

AU - Lu, Xin

AU - Chakraborty, Pulak K.

AU - Chugani, Diane C.

AU - Chugani, Harry T.

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N2 - 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 11C-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 11C-doxepin more accessible for clinical studies.

AB - 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 11C-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 11C-doxepin more accessible for clinical studies.

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KW - Doxepin

KW - Histamine H1 receptor

KW - PET

KW - Radiosynthesis

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