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


METHODS
Athymic nude rodents were treated with 1.25 x 10(10) particles of adenovirus-BMP-2 (Ad-BMP-2) (treatment group) or adenovirus-beta-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.


CONCLUSIONS
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.
Varady
Peter
P
Department of Neurosurgery, University of Virginia Health System, Health Sciences Center, Charlottesville 22908, USA.
Li
Jin Zhong
JZ
Alden
Tord D
TD
Kallmes
David F
DF
Williams
Mark B
MB
Helm
Gregory A
GA
D000256:Adenoviridae; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D010012:Osteogenesis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D011923:Rats, Nude; D013669:Technetium Tc 99m Medronate; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D019275:Radiopharmaceuticals; D016212:Transforming Growth Factor beta; D013669:Technetium Tc 99m Medronate