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Evaluation of New Bone Formation in Normal and Osteoporotic Rats with a 3-mm Femur Defect: Functional Assessment with Dynamic PET-CT (dPET-CT) Using 2-Deoxy-2-[18F]Fluoro-d-glucose (18F-FDG) and 18F-Fluoride

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Abstract

Purpose

The aim of the current study was to assess the formation of new bone in a 3-mm created defect in the femur and its adjacent bone tissue in osteoporotic and normal animals. The assessment is based on bone remodeling and glucose metabolism in a rat model with a 3-mm created defct in the femur using 18F-fluoride and 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) as tracers for dynamic PET-CT (dPET-CT). The 18F-fluoride PET data were compared with those of 18F-FDG.

Procedures

Osteoporosis was induced by ovariectomy and a calcium restricted diet in each rat (n = 7). Alternatively, a sham operation was performed in the control group (n = 8). After 3 months, all rats were operated to create a 3-mm defect using an oscillating saw in the distal metaphyseal femur, which was internally fixed with a metal plate. Eighteen weeks after osteoporosis induction and 6 weeks following femoral surgery, dPET-CT studies scan were performed with 18F-FDG and 18F-fluoride. Following PET data acquisition, standardized uptake values (SUVs) were calculated from the tracer concentration values. Then, a two-tissue compartmental learning-machine model was applied to the data for the calculation of the compartment parameters (K1-k4, VB, Ki). Furthermore, a non-compartmental model based on the fractal dimension was applied for quantitative analysis of both groups and both tracers. Finally, multivariate analysis was performed for the statistical analysis of the kinetic data.

Results

The values for K1 and Ki were higher in the osteoporotic rats than in the control group. Ki and K1 of 18F-fluoride in the adjacent bone tissue differ significantly based on the Wilcoxon rank-sum test for the osteoporotic and control group (p < 0.05). The sensitivity and the negative predictive value (NPV) based on linear discriminant analysis was high with a value of 100 % for both tracers and both evaluated regions (defect and adjacent bone tissue) when comparing control and osteoporotic rats. The overall accuracy with 18F-FDG was generally higher than that with 18F-fluoride for both evaluated regions for the control and osteoporotic rats based on a multiparameter evaluation.

Conclusion

In this study, the changes in tracer kinetics accurately discriminated differences in the created defect in the femur and its adjacent bone tissue between osteoporotic and control rats.

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Abbreviations

18F-FDG:

2-deoxy-2-[18F]fluoro-d-glucose

dPET-CT:

dynamic PET-CT

BMD:

bone mineral density

DEXA:

dual energy X-ray absorptiometry

SUV:

standardized uptake value

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Acknowledgements

This study is part of the Sonderforschungsbereich-Transregio 79 (SFB-TR 79) and was in part financially supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG).

Conflict of interest

The authors declare that they have no conflict of interest

Author information

Authors and Affiliations

  1. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Caixia Cheng, Antonia Dimitrakopoulou-Strauss, Leyun Pan & Ludwig G. Strauss

  2. Department of Trauma Surgery, University Hospital Giessen-Marburg GmbH, Giessen, Germany

    Volker Alt, Ulrich Thormann & Reinhard Schnettler

  3. Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany

    Klaus Weber

Authors
  1. Caixia Cheng
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  2. Volker Alt
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  8. Ludwig G. Strauss
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Correspondence to Caixia Cheng.

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Cheng, C., Alt, V., Dimitrakopoulou-Strauss, A. et al. Evaluation of New Bone Formation in Normal and Osteoporotic Rats with a 3-mm Femur Defect: Functional Assessment with Dynamic PET-CT (dPET-CT) Using 2-Deoxy-2-[18F]Fluoro-d-glucose (18F-FDG) and 18F-Fluoride. Mol Imaging Biol 15, 336–344 (2013). https://doi.org/10.1007/s11307-012-0592-9

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