A dual positron emission tomography (PET) tracer study with [18F]fluoride and the freely diffusible tracer [(15)O]H2O was performed to measure the capillary transport of [18F]fluoride and to evaluate the potential of [18F]fluoride ion PET to quantitate bone blood flow. Under the condition of a high predictable single-pass extraction fraction (E(F)) for [18F]fluoride, the [18F]fluoride ion influx transport constant (K1F), derived from kinetic [18F]fluoride ion PET measurements, can be used to estimate bone blood flow. Bone blood flow was measured in vertebral bodies by dynamic [(15)O]H2O PET during continuous ventilation with N2O, O2, and Isoflurane (FiO2 = 0.3) in seven adult mini pigs, followed by dynamic [18F]fluoride ion PET. The mean blood flow measured by [(15)O]H2O (FlowH2O) was 0.145 +/- 0.047 ml x minute(-1) x ml(-1) and the mean K1F was 0.118 +/- 0.031 ml x minute(-1) x ml(-1), respectively (mean +/- SD). Regional analysis showed excellent agreement between FlowH2O and K1F at low flow and a significant underestimation of flow by K1F relative to FlowH2O in regions of normal and elevated flow. The observed relationship between parameters followed the Renkin-Crone distribution. The permeability-surface product was determined as 0.25 minute(-1) for vertebral bodies consisting of a mixture of trabecular and cortical bone. We conclude that [18F]fluoride ion PET can be used to estimate bone blood flow in low and normal flow regions, as long as the flow dependency of the E(F) is taken into consideration. Above blood flow values of 0.2 to 0.35 ml x minute(-1) x ml(-1), the magnitude of K1F is increasingly independent on blood flow because diffusion limits tracer transport.