Shining dead bone-cause for cautious interpretation of [¹⁸F]NaF PET scans

Background and purpose - [¹⁸F]Fluoride ([¹⁸F]NaF) PET scan is frequently used for estimation of bone healing rate and extent in cases of bone allografting and fracture healing. Some authors claim that [¹⁸F]NaF uptake is a measure of osteoblastic activity, calcium metabolism, or bone turnover. Based on the known affinity of fluoride to hydroxyapatite, we challenged this view. Methods - 10 male rats received crushed, frozen allogeneic cortical bone fragments in a pouch in the abdominal wall on the right side, and hydroxyapatite granules on left side. [¹⁸F]NaF was injected intravenously after 7 days. 60 minutes later, the rats were killed and [¹⁸F]NaF uptake was visualized in a PET/CT scanner. Specimens were retrieved for micro CT and histology. Results - MicroCT and histology showed no signs of new bone at the implant sites. Still, the implants showed a very high [¹⁸F]NaF uptake, on a par with the most actively growing and remodeling sites around the knee joint. Interpretation - [¹⁸F]NaF binds with high affinity to dead bone and calcium phosphate materials. Hence, an [¹⁸F]NaF PET/CT scan does not allow for sound conclusions about new bone ingrowth into bone allograft, healing activity in long bone shaft fractures with necrotic fragments, or remodeling around calcium phosphate coated prostheses.