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Journal of Nuclear Medicine

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Meeting ReportMolecular Targeting Probes Track

Autmoated radiosynthesis of 18F-THK-5351 using the Sofie ELIXYS

Tobey Betthauser, Paul Ellison, Dhanabalan Murali, Patrick Lao, Todd Barnhart, Shozo Furumoto, Nobuyuki Okamura, Robert Nickles, Sterling Johnson and Bradley Christian
Journal of Nuclear Medicine May 2017, 58 (supplement 1) 338;
Tobey Betthauser
6University of Wisconsin-Madison Madison WI United States
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Paul Ellison
3University of Wisconsin Madison WI United States
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Dhanabalan Murali
3University of Wisconsin Madison WI United States
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Patrick Lao
4University of Wisconsin at Madison Madison WI United States
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Todd Barnhart
3University of Wisconsin Madison WI United States
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Shozo Furumoto
1CYRIC, Tohoku University Sendai Japan
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Nobuyuki Okamura
2Tohoku University School of Medicine Sendai Japan
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Robert Nickles
5University of Wisconsin Medical Physics Madison WI United States
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Sterling Johnson
6University of Wisconsin-Madison Madison WI United States
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Bradley Christian
6University of Wisconsin-Madison Madison WI United States
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Abstract

338

Objectives: Positron emission tomography (PET) radiopharmaceutical 18F-THK-5351 has recently been developed for in vivo investigation of neurofibrillary tau protein deposits observed in neurodegenerative diseases, including Alzheimer’s disease. Increasing interest in this research area necessitates reliable routine production of 18F-THK-5351 with processes that minimize radiation dose to radiochemists and provide sufficient radiochemical yields. The goal of this work was to automate the radiochemical synthesis, purification and formulation of 18F-THK-5351 in preparation for regular production.

Methods: Cleaning and radiosynthesis procedures were developed involving cassettes 1 and 2, and HPLC injection components of the Sofie ELIXYS automated radiochemical synthesis module. The radiosynthesis procedure included preparation of 18F-fluoride in K222/K2CO3 via ion exchange from cyclotron produced 18F in 18O-H2O, azeotropic distillation with acetonitrile, nucleophilic substitution of THK-5352, hydrolysis of the protecting group, neutralization, dilution and solid phase extraction of crude reaction product, and injection onto semi-preparative HPLC. Labview software was written and hardware was developed to perform radioHPLC data acquisition, HPLC fraction collection management, gross dilution of the collected HPLC fraction, solid phase extraction, and final formulation of 18F-THK-5351. Five production runs were carried out starting with 11- 37 GBq 18F-fluoride in 18O-H2O and precursor masses of 0.2-0.5 mg. Radiochemical yields were determined for formulated 18F-THK-5351 product. Analytical HPLC was performed to determine radiochemical and chemical purity, as well as specific activity. Gas chromatography was performed to test for residual purification solvents.

Results: Decay-corrected radiochemical yields determined from the end of bombardment to formulation were 14±5% and 21±2% for starting precursor masses of 0.2 and 0.5 mg, respectively with an average synthesis and final formulation time of 91±8 minutes. The average radiosynthesis procedure was 55±4 minutes using the ELIXYS. Formulated yields, chemical and radiochemical purity, and specific activity are given in table 1. All batches were below the U.S. Pharmacopeial Convention residual solvent limit for acetonitrile, which was present in only two batches in trace quantities.

Conclusion: The Sofie ELIXYS combined with an HPLC purification and final formulation module can be used to routinely synthesize 18F-THK-5351 in 90 minutes with sufficient yields for multiple injection studies. Work is ongoing to reduce synthesis times, improve radiochemical yields, and validate these methods for cGMP production. Acknowledgements: The Phelps Family Foundation and Sofie Biosciences are gratefully recognized.

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Journal of Nuclear Medicine
Vol. 58, Issue supplement 1
May 1, 2017
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Autmoated radiosynthesis of 18F-THK-5351 using the Sofie ELIXYS
Tobey Betthauser, Paul Ellison, Dhanabalan Murali, Patrick Lao, Todd Barnhart, Shozo Furumoto, Nobuyuki Okamura, Robert Nickles, Sterling Johnson, Bradley Christian
Journal of Nuclear Medicine May 2017, 58 (supplement 1) 338;

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Autmoated radiosynthesis of 18F-THK-5351 using the Sofie ELIXYS
Tobey Betthauser, Paul Ellison, Dhanabalan Murali, Patrick Lao, Todd Barnhart, Shozo Furumoto, Nobuyuki Okamura, Robert Nickles, Sterling Johnson, Bradley Christian
Journal of Nuclear Medicine May 2017, 58 (supplement 1) 338;
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