Combination of MRI and 99mTc-NTP 15-5 Scintigraphy for the Assessment of Intervertebral Disk Degeneration and Tissue Engineering

Abstract

Introduction Intervertebral disk degeneration is one of the leading causes of low back pain. The development of regenerative cell-based biotherapies for degenerated IVD has recently been contemplated. To evaluate the preclinical relevance of such therapies, animal models combined with longitudinal imaging methods such as MRI are currently used. However, facing the limitations of MRI and to further decipher the early process of IVD degeneration, innovative radio imaging approaches are considered promising. In this context, we were interested in determining whether a scintigraphic imaging approach using a specific proteoglycan radiotracer (99mTc-NTP 15-5) could be instrumental to assess the biofunctionality of IVD extracellular matrix. Materials and Methods New Zealand white rabbits (1-, 6-, 12- and 30-month-old; n = 3 for each age) were used. Early aging of lumbar IVD was determined by MRI and scintigraphic analysis. MRI images were analyzed using T2-weighted signal intensity (T2wsi) and scored according to the Pfirrmann grading. In a first set of experiments, scintigraphic analyses were performed to assess the kinetic distribution in 12-month old rabbits. Ratio IVD on muscle fixation was measured. The distribution of 99 mTc-NTP-15-5 in IVD was evaluated by in vivo scintigraphic imaging (BigSpace Gamma Imager) on three rabbits of each age. Results MRI assessments of rabbit IVDs reveal as a function of age, a grading decrease in IVD signal intensity (T2wsi) associated with an increase in Pfirrmann grade. These data indicate the existence of an aging/degeneration process of rabbit IVD. As a function of escalating ages, a differential uptake of 99 mTc-NTP 15-5 in IVD was observed. Uptake was maximal at 1 month of age, and was followed by a dramatic decrease as early as 6 months (approximately 50% of radioactive signal). After 6 months, the intensity of decrease was less pronounced (approximately 10% of radioactive signal). Conclusion These in vivo results highlight the interest of combining 99 mTc-NTP-15-5 scintigraphic imaging of proteoglycans with MRI. Whereas MRI T2wsi reflects the hydration level, 99 mTc-NTP-15-5 scintigraphy allowed the functional assessment of IVD at the proteoglycan level. Such multi-imaging approach could be useful for the longitudinal study of engineered IVD following the intradiscal transplantation of mesenchymal stem cells using an injectable biomaterial. In addition, the use of scintigraphy imaging in human should be paid further attention particularly to detect the early IVD degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared