[18F]Fluoride uptake in various bone types and soft tissues in rat

Abstract 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 if the knowledge of [18F]fluoride pharmacokinetics would increase our understanding of the biodistribution of 18F-labelled tracers and clinical interpretation of [18F]NaF PET? 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, Ki, Ki/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, and the same applies when [18F]NaF is used in human bone or calcification studies.