Molecular imaging characterization of Distraction Osteogenesis model

  • Balasse Laure
  • Roseren Flavy
  • Moyon Anais
  • Fernandez Samantha
  • Garrigue Philippe
  • Hache Guillaume
  • Pithioux Martine
  • Guillet Benjamin


Aim/Introduction: Distraction osteogenesis (DO) is a surgical procedure widely used for limb lengthening to treat limb length discrepancy. DO procedure is divided into three distinct phases. The latency period starts after callotasis surgery (A), followed by the distraction period (B). When the desired elongation is reached, the external fixator is then locked, and consolidation period is initiated (C). To date, if limb lengthening is efficient, the duration of phase C needed to remove external fixator, remains hard to set, causing a high risk of fracture. This work aimed to characterize, using molecular imaging, callus regeneration, angiogenesis and osteoblastic activity in rat model of DO during Phases A, B and C. Materials and Methods: A DO rat model (1) were applied to 6 male rats. Animals were weekly monitored during the phases A (6 days), B (10 days), C (6 weeks) by μCT, μTEP and μSPECT to quantify the bone density, angiogenesis and bone metabolism. Angiogenesis were longitudinally evaluated using 10±0.5 MBq of [68Ga]-RGD. PET images were acquired 1h after injection on Mediso-NanoPET-CT. Bone metabolism were longitudinally monitored using 30±1.5 MBq of [99mTc]-HMDP. Planar SPECT images were acquired 4h after injection on Mediso-NanoSPECT-CT. Quantitative region-of-interest (ROI) analysis of PET and SPECT images were performed with Vivoquant software (Invicro®) and tissue uptake values presented as ratio of fractured bone on contralateral bone (i/c). Results: Molecular imaging showed that activation of angiogenesis and osteogenesis both started on Day 6 after the surgery during PhaseA, increased progressively during Phase B up to the end of the phase to an C : i/c ratios of 5.6±1.2 and 2.59±0.4 respectively for [68Ga]-RGD and [99mTc]-HMDP imaging. Then [68Ga]-RGD TEP signal start to decrease and normalized 2 weeks after the end of phase C and [99mTc]-HMDP SPECT signal normalized 4 weeks after the end of phase C. Conclusion: This is the first report of molecular imaging characterization of DO model. DO induced strength and sustained activations of both angiogenesis and osteogenesis that persists several weeks after distraction. Osteogenesis activation is more sustained than angiogenesis. This work shows that molecular imaging can be an efficient imaging tool to evaluate new optimization of DO procedure and that PET and SPECT imaging could be a valuable tool to determine whether the bone reconstruction phase should be extended and decrease the risk of fracture for which occurrence after removal remain frequent. References: (1) M. Pithioux and al., 2