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Assessment of Porcine Bone Metabolism by Dynamic [¹⁸F]Fluoride Ion PET: Correlation with Bone Histomorphometry

Departments of General Surgery and Nuclear Medicine and Section of Radiopharmacy, University of Tübingen, Tübingen, Germany

The aim of this study was to quantify regional bone blood flow and [¹⁸F]fluoride ion influx with [¹⁸F]fluoride ion PET and correlate the results with specific static and dynamic indices of bone metabolism in healthy pigs. Methods: During continuous ventilation (fractional concentration of oxygen in inspired gas = 0.3), dynamic PET scans 120 min in duration were obtained for 9 mini pigs after intravenous injection of 10.0 ± 1.2 MBq (mean ± SD) of [¹⁸F]fluoride ion per kilogram of body weight. Iliac crest bone biopsies were performed immediately before the PET scan to determine static and dynamic indices of bone metabolism (i.e., the mineral apposition rate) by bone histomorphometry. Kinetic rate constants describing influx (K₁) and efflux (k₂) of [¹⁸F]fluoride as well as chemisorption and incorporation of [¹⁸F]fluoride (k₃) and reverse transport (k₄) were determined for 6 vertebral bodies in each animal. Blood flow estimates (f) were derived from K₁ values corrected for the permeability–surface area product using a previously derived correction algorithm. A rate constant describing the net forward transport rate of fluoride (K_i) and the fluoride volume flux (K_flux) derived from a 2-tissue-compartment model was calculated and compared with the results of Patlak graphic analysis (K_pat). Results: A significant correlation was found between mineral apposition rate and K_i (P < 0.005), K_flux (P < 0.01), K_pat, K₁, and f (P < 0.05). The values of f, K_i, K_flux, and K_pat did not correlate significantly with other static or dynamic histomorphometric indices or with age, serum alkaline phosphatase, or parathyroid hormone levels. The values of f and K_i correlated linearly (y = 0.023 + 0.32x; r² = 0.74; P < 0.001). Conclusion: PET bone studies using [¹⁸F]fluoride ion provide quantitative estimates of bone blood flow and metabolic activity that correlate with histomorphometric indices of bone formation in the normal bone tissue of the mini pig. Therefore, it seem reasonable to assume that [¹⁸F]fluoride ion PET can reduce the number of invasive bone biopsies, thus facilitating follow-up of patients with metabolic bone diseases.

Key Words: [¹⁸F]fluoride ion PET • bone metabolic activity • bone histomorphometry • bone blood flow • quantitative imaging

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