Automated production of [¹⁸F]F^- and [¹⁸F]FDG at the University of Oklahoma Health Sciences Center (OUHSC)

Objectives The OUHSC-College of Pharmacy has installed and commissioned the first Biomarker Generator comprising an automated cyclotron-synthesis box-quality control system for on-site manufacture of [¹⁸F]F^- and [¹⁸F]FDG. Performance, reliability and safety of the system for production of 'Dose on demand' was tested over several months.

Methods The Biomarker Generator is a 7.5 MeV positive-ion cyclotron coupled with a customized Chemistry Production Module. Automated QC tests were performed on each dose. The HPLC-based analytical methods were validated against USP methods of quality control. The entire hardware was controlled by a National Instruments DAQ using LabView software. A customized and scaled down monitoring system was installed for radiation safety purposes, in view of the self-shielded production of limited quantities of [¹⁸F]F^- per run.

Results After initial installment and optimization, [¹⁸F]F^- production has been consistent since Mar 2011 with a maximum production of 400 to 450 mCi/day (≈ 1 mCi/3.5 μA.min). The current target window has held up for over 25 weeks against > 400 bombardment cycles. [¹⁸F]FDG production has been consistent since Jun 2012 with an average of six doses/day in automated synthesis mode (RCY≈ 50%) . The release criteria included USP-specified limits for pH, residual solvents, kryptofix, radiochemical purity/identity and filter integrity test. When injected in a mouse model of xenograft tumor, the [¹⁸F]FDG produced in the Biomarker Generator was found to be bioequivalent to the commercially available [¹⁸F]FDG. The entire operation was deemed satisfactory from radiation safety viewpoint.

Conclusions Automated and safe production and quality control of '[¹⁸F]FDG dose on demand' has been accomplished by the World's first installed Biomarker Generator. The implementation of a GMP quality system is under way towards the ANDA submission and first clinical use of [¹⁸F]FDG. Detail production, QC and radiation safety aspects will be presented.