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Application of F-18-Sodium Fluoride (NaF) Dynamic PET-CT (dPET-CT) for Defect Healing: A Comparison of Biomaterials in an Experimental Osteoporotic Rat Model

Caixia Cheng, Volker Alt, Leyun Pan, Ulrich Thormann, Reinhard Schnettler, Ludwig G. Strauss, Sascha Heinemann, Matthias Schumacher, Michael Gelinsky, Berthold Nies, Antonia Dimitrakopoulou-Strauss

Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany

Med Sci Monit 2014; 20:1942-1949

DOI: 10.12659/MSM.891073

Available online:

Published: 2014-10-15

Background: The aim of the current study was to measure and compare the effect of various biomaterials for the healing of osteoporotic bone defects in the rat femur using 18F-sodium fluoride dPET-CT.
Material and Methods: Osteoporosis was induced by ovariectomy and a calcium-restricted diet. After 3 months, rats were operated on to create a 4-mm wedge-shaped defect in the distal metaphyseal femur. Bone substitution materials of calcium phosphate cement (CPC), composites of collagen and silica, and iron foams with interconnecting pores were inserted. Strontium or bisphosphonate, which are well known for having positive effects in osteoporosis treatment, were added into the materials. Eighteen weeks after osteoporosis induction and 6 weeks following femoral surgery, dPET-CT studies scan were performed with 18F-Sodium Fluoride. Standardized uptake values (SUVs) and a 2-tissue compartmental learning-machine model (K1-k4, vessel density [VB], influx [ki]) were used for quantitative analysis.
Results: k3, reflecting the formation of fluoroapatite, revealed a statistically significant increase at the biomaterial-bone interface due to the Sr release from strontium-modified calcium phosphate cement (SrCPC) compared to CPC, which demonstrated enhanced new bone formation. In addition, k3 as measured in the porous scaffold silica/collagen xerogel (Sc-B30), showed a significant increase based on Wilcoxon rank-sum test (p<0.05) as compared with monolithic silica/collagen xerogel (B30) in the defect region. Furthermore, ki, reflecting the net plasma clearance of tracer to bone mineral measured in the iron foam with coating of the bisphosphonate zoledronic acid (Fe-BP), was enhanced as compared with plain iron foam (Fe) in the defect region.
Conclusions: k3 was the most significant parameter for the characterization of healing processes and revealed the best differentiation between the 2 different biomaterials. PET scanning using 18F-sodium fluoride seems to be a sensitive and useful method for evaluation of bone healing after replacement with these biomaterials.

Keywords: Biocompatible Materials, Animals, Disease Models, Animal, Multimodal Imaging, Osteoporosis - pathology, Positron-Emission Tomography, Rats, Rats, Sprague-Dawley, Sodium Fluoride - administration & dosage, Tomography, X-Ray Computed