Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [(15)O]H(2)O and [(18)F]fluoride ion positron emission tomography.
Previously, we identified a parathyroid hormone-related high-turnover bone disease after gastrectomy in mini pigs. Dynamic [(18)F]fluoride ion positron emission tomography (PET) revealed that bone metabolism was significantly increased, but that bone blood flow derived from permeability-surface area product (PS product)-corrected K(1) values was not. Since bone blood flow and metabolism are coupled in normal bone tissues, we hypothesised that the capillary permeability and/or surface area might be altered in high-turnover bone disease. The "true" bone blood flow ( f(H2O)) was measured in vertebral bodies by dynamic [(15)O]H(2)O PET, followed by a 120-min dynamic [(18)F]fluoride ion PET study, 6 months after total gastrectomy (n=5) and compared with results in sham-operated animals (n=5). Estimates for bone blood flow based on PS-corrected K(1) values (f) and the net uptake of fluoride in bone tissue (K(i)), representing the bone metabolic activity, were calculated using standard compartmental modelling and non-linear fitting. Gastrectomy was followed by a significant elevation of K(i) and k(3) ( P<0.05), which was mainly caused by an increase of the fraction of bound tracer in tissue (P<0.01). In contrast, f(H2O), f, the single-pass extraction fraction of [(18)F]fluoride (E) and the volume of distribution (DV) of [(18)F]fluoride were not significantly different between groups. In both groups, a coupling of the mean f(H2O) and K(i) values was found, but the intercept with the y-axis was higher in high-turnover bone disease. It is concluded that in high-turnover bone disease following gastrectomy, the PS product for [(18)F]fluoride remains unchanged. Therefore, even in high-turnover bone diseases, [(18)F]fluoride ion PET can provide reliable blood flow estimates (f), as long as a proper PS product correction is applied. The increased bone metabolism in high-turnover bone disease after gastrectomy is mainly related to an up-regulation of the amount of ionic exchange of [(18)F]fluoride with the bone matrix, while tracer delivery remains unchanged.
Piert
Morand
M
Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, Germany. m.piert@lrz.tu-muenchen.de
Machulla
Hans-Jürgen
HJ
Jahn
Michael
M
Stahlschmidt
Anke
A
Becker
Georg A
GA
Zittel
Tilman T
TT
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D001842:Bone and Bones / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D005743:Gastrectomy / Q000009:adverse effects; D010104:Oxygen Radioisotopes / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013131:Spine / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism*; D013223:Statistics as Topic; D013552:Swine; D014867:Water
D005462:Fluorine Radioisotopes; D010104:Oxygen Radioisotopes; D019275:Radiopharmaceuticals; D014867:Water