Inhibition of viability of microorganisms in [¹⁸F]-labeled radiopharmaceuticals

Good manufacturing practice (GMP)-compliant production of radiopharmaceuticals for parenteral application requires great efforts in maintenance of clean room infrastructure and equipment in order to reliably guarantee the constant hygienic quality of the product (sterility). Terminal sterilization of the product is not always possible due to short half-life or due to thermal instability of the compound. The typical method for sterilization in these cases is sterile filtration prior to dispensing (distribution of product solution from bulk to patient vials). Therefore, aseptic processing techniques have to be in place in order to ensure sterility. Still, there remains some risk of microbial contamination of the product, and hence a risk for the patient to suffer from infection. Due to the short half-life of the labeling radionuclides, this aspect is aggravated by only retrospectively possible testing for sterility. This work investigated the potential of [¹⁸F]-radiation to intrinsically inactivate microorganisms (MO) that might have slipped through the aseptic process.

Defined numbers of viable cells of different bacterial strains and molds were incubated with defined amounts of [¹⁸F]-activity. After decay of radiation the number of surviving viable cells was determined, D₁₀-values were calculated and evaluated.

The MOs tested exhibit a broad range of [¹⁸F]-radiation susceptibility, D₁₀-values range from a sensitive 114MBq/mL (46Gy) to a durable 2,048MBq/mL (790Gy).

The intrinsic [¹⁸F]-radiation in radiopharmaceuticals is no safe measure to generally ensure sterility of the product solution in terms of "autosterilization", because of dependence on various parameters.

This work presents for the first time experimental data on the influence of [¹⁸F]-radiation on MOs. The results suggest, that aseptic processing techniques are essential and that results of determination of sterility in radiopharmaceuticals should be considered with care (emphasis on importance of media fill campaigns).