Automated Manufacture of [¹⁸F]FMISO in the BG 75 system. Synthesis and Purification using Solid Phase Extraction.

Objectives 1) Optimization of F-18 incorporation in 1H-imidazole-1-propanol, 2-nitro-β-[(tetrahydro-2H-pyran-2-yl)oxy]-, 4-methylbenzenesulfonate (ester). 2) [¹⁸F]FMISO purification I. Radiochemical Purity 3) [¹⁸F]FMISO purification II. Chemical Purity 4) Proof of concept for automation of quality control tests for [¹⁸F]FMISO using the BG 75 system.

Methods [¹⁸F]FMISO was produced using the BG 75 system using a single dose format, using a synthesis card. Temperature, time, nature of phase transfer catalyst and solvent were explored to optimize radiochemical yield. Umpurified samples were passed through solid phase extraction resins and later sterilized by filtration. Key quality controls were tested according to conventional tests.

Results Up to five (5) doses of sterile [¹⁸F]FMISO were produce in a single day. All key quality control requirements tested were met and the radiochemical yield for doses was in the range 35 to 45%. Proof of concept for automatization in quality control: pH, residual solvents, radiochemical identity and filter integrity tests was performed.

Conclusions The system BG 75 can produce sterile doses of [¹⁸F]FMISO on demand with appropriate radiochemical yield, promising results on the automated quality controls points toward an automated production of [¹⁸F]FMISO including synthesis and purification.

Research Support None