The chemically stable anion of Fluorine-18-Fluoride is a bone-seeking radiotracer in skeletal imaging. [F]NaF has an affinity to deposit at areas where the bone is newly mineralizing. Many studies have [F]NaF PET to measure bone metabolism at the hip, lumbar spine, and humerus. [F]NaF is taken-up in an exponential manner representing the equilibration of tracer with the extracellular and cellular fluid spaces with a half-life of 0.4 hours, and with kidneys with a half-life of 2.4 hours. The single passage extraction of [F]NaF in bone is 100%. After an hour, only 10% of the injected activity remains in the blood.
F- ions are considered to occupy extracellular fluid spaces because, firstly, they equilibrate with transcellular fluid spaces and secondly, they are not entirely extracellular ions. Fluoride undergoes equilibrium with hydrogen fluoride, which has a high permeability allowing fluoride to cross the plasma blood membrane. The fluoride circulation in red blood cells accounts for 30%. However, it is freely available to the bone surface for uptake because the equilibrium between erythrocytes and plasma is much faster than the capillary transit time. This is supported by studies reporting 100% single-passage extraction of whole-blood F- ion by bone and the rapid release of F- ions from erythrocytes with a rate constant of 0.3 per second.
[F]NaF is also taken-up by immature erythrocytes in the bone marrow, which plays a role in fluoride kinetics. The plasma protein binding of [F]NaF is negligible. [F]NaF renal clearance is affected by diet and pH level, due to its re-absorption in the nephron, which is mediated by hydrogen fluoride. However, large differences in urine flow rate are avoided for controlled experiments by keeping patents well hydrated.
The exchangeable pool and the size of the metabolically active surfaces in bones determines the amount of tracer accumulated or exchanged with bone extracellular fluid, chemisorption onto hydroxyapatite crystals to form fluorapatite, as shown in Equation-1:
                                                                           Equation-1
Fluoride ions from the crystalline matrix of bone are released when the bone is remodelled, thus providing a measure of the rate of bone metabolism.