Background: In the development of new ¹⁸F-labelled tracers, it is important to assess the amount of released [¹⁸F]fluoride taken up in the bones of experimental animals because all ¹⁸F-labelled PET-tracers are prone, to lesser or higher degree, to undergo defluorination, with subsequent release of [¹⁸F]fluoride during scanning. However, the pharmacokinetics of [¹⁸F]fluoride in bones and other organs of healthy rats have not been well documented in a comprehensive manner. We aimed to study pharmacokinetics of [¹⁸F]NaF in rats in order to increase our understanding of the biodistribution of [¹⁸F]fluoride originating from defluorination of ¹⁸F-labelled tracers. We studied [¹⁸F]fluoride uptake in Sprague Dawley rat bones, including the epiphyseal parts of the tibia and radius, the mandible, ilium, lumbar vertebrae, costochondral joints, tibia, radius, and ribs, with 60-min in vivo PET/CT imaging. Kinetic parameters, K₁, K_i, K_i/K₁, and k₃ were calculated with a three-compartment model. In addition, separate groups of male and female rats were studied with ex vivo bone and soft tissue harvesting and gamma counting over a 6-h period.

Results: [¹⁸F]fluoride perfusion and uptake varied among the different bones. [¹⁸F]fluoride uptake was higher in trabecular bones, due to high perfusion and osteoblastic activity, compared to cortical bones. In soft tissues, the organ-to-blood uptake ratios increased over time in the eyes, lungs, brain, testes, and ovaries during the 6 h study period.

Conclusion: Understanding the pharmacokinetics of [¹⁸F]fluoride in various bones and soft tissues is highly useful for assessing ¹⁸F-labelled radiotracers that release [¹⁸F]fluoride.