A preclinical platform that combines dynamic scintigraphy, SPECT and CT imaging towards bone defect diagnosis and therapy assessment
M. Rouchota1, E. Campodoni5, E. Dermisiadou3, E. Fragogeorgi4, S. Xanthopoulos4, I. Pilatis1, I. Panopoulos3, M. Sandri5, M. Velez5, P. Bouziotis4, G. Loudos1
1 BIOEMTECH, Lefkippos Attica Technology Park, NCSR “Demokritos”, Ag. Paraskevi-Athens, Greece
2 Institute of Science and Technology for Ceramics (ISTEC), CNR, Faenza (RA), Italy
3 Department of Diagnostic Imaging Unit (Alphavet), New Kifissia, Athens, Greece
4 Institute of Nuclear & Radiological Sciences, Technology, Energy & Safety (INRASTES), NCSR ‘‘Demokritos”, Ag. Paraskevi-Athens, Greece
5 Catalysis and Oil-chemistry Institute (CSIC), Madrid, Spain
Abstract
Bone defects are one of the leading pathologies in the developing world and challenging to assess through non-invasive methods. The objective of the this study, is to create a preclinical platform, to non-invasively monitor bone defects and therapy efficiency, by exploiting complementary imaging techniques. Towards this scope, healthy mice were first imaged with the clinically approved tracer [99mTc]-MDP. Imaging was performed in three stages: (a) first with live, dynamic scintigraphy (γ-eyeTM, BIOEMTECH) to check and establish the best accumulation time points of the tracer and the main possible defect regions. Then, (b) high-resolution imaging was performed with CT imaging (X-CUBE, Molecubes) for the detailed anatomic illustration and (c) tomographic SPECT imaging (γ-CUBE, Molecubes) for the detailed metabolic function representation.
This platform was then exploited on a mouse calvarial defect model. Two symmetrical calvarial bone defects, 1.5 mm in diameter each, were created in female Swiss mice. Gaps were monitored weekly through SPECT/CT imaging, using [99mTc]-MDP for 5 weeks. Defects created on the left part of the mouse skull were left unfilled (control group), whereas those on the right part were filled with mineralized horse collagen scaffold materials (HA/Coll). For the HA/Coll treated defect, a peak in metabolic activity was noted at week 1 post-surgery and the defect was filled by newly developed bone tissue by week 3 post-surgery. In contrast, the metabolic activity at the control defect area was stable but significantly lower and a complete healing was not observed even up to week 5 post-surgery.
These results highlight the complementary information that can be exported through this platform: fast establishment of the best accumulation time and defect regions through live, dynamic scintigraphy, then high-resolution functional information on the metabolic activity that predicts bone formation, through SPECT imaging and high-resolution anatomic information that shows the actual bone being formed, through CT imaging.
The presented preclinical platform can serve as a strong non-invasive tool, to monitor bone defects and to evaluate both novel synthetic bone implants and therapy schemes aiming to increase bone metabolic activity and healing of a wide range of bone pathologies.