CT and radionuclide study of BMP-2 gene therapy-induced bone formation

Rationale and Objectives. Gene therapy techniques have the potential to treat numerous diseases, from cancer to diabetes. One promising application is the use of bone morphogenetic protein (BMP) gene transfer to induce bone formation. Previous studies have demonstrated that both direct and ex vivo BMP gene therapy have the capacity to initiate the normal endochondral pathway, leading to rapid mature bone formation. In the present study, computed tomography (CT) and radionuclide imaging was used to assess bone formation induced by BMP gene therapy accurately and noninvasively. Materials and Methods. Athymic nude rodents were treated with 1.25 × 10¹⁰ particles of adenovirus-BMP-2 (Ad-BMP-2) (treatment group) or adenovirus-β-gal (control group). At various intervals after treatment, the animals underwent CT, planar digital radiography, and planar radionuclide scintigraphic imaging. Results. Radionuclide scintigraphy clearly demonstrated active bone deposition that began as early as 15 days after treatment and peaked at approximately 36 days, only at the Ad-BMP-2 injection sites. CT clearly demonstrated ectopic bone induction over time at the Ad-BMP-2 treatment sites, in perfect correlation with the scintigraphic findings. Conclusion. This study clearly illustrates that gene therapy-induced osteogenesis can be studied with multimodality imaging and supports the use of these approaches in future preclinical and clinical studies.