Micro-CT combined with bioluminescence imaging: a dynamic approach to detect early tumor-bone interaction in a tumor...

Prostate cancer (CaP) cells possess high affinity for bone marrow and predilection to induce bone metastasis. Although the end result of metastasis is predominantly osteoblastic, most patients present mixed lesions with osteolytic component which could initiate and precede bone formation. A precise characterization of tumor-induced bone resorption is thus necessary for early evaluation of therapeutic efficiency. Herein, we investigate the advantage of combining micro-computed tomography (microCT) and in vivo bioluminescence imaging (BLI) to determine the kinetics of the intraosseous CaP growth and bone lesions appearance in an experimental murine model. To mimic established osteolytic bone metastasis, the left tibiae of SCID mice were injected with the human CaP cell line PC-3 expressing luciferase (PC-3 Luc). Noninvasive monitoring of tumor progression was followed weekly by BLI during 4 weeks and bone morphometric parameters were quantified by microCT. Data were compared with conventional radiological and histological analyses. While BLI monitoring in vivo revealed an exponential growth of PC-3 Luc after 2 weeks, a decrease of bone density and bone mineral content was evidenced by microCT as early as 7 days post-injection, reaching significant values at day 21 (30% and 25% loss, respectively), compared with mock-injected controls. Enhanced osteoclast TRAP activity was observed during the first two weeks, highlighting an active interaction between low proliferative PC-3 cells and osteoclasts at the early stage of tumor establishment in bone. Tumor growth detected by BLI was tightly correlated to the osteolysis assessed by microCT (p<0.05). Our results show that the combination of microCT and BLI applied to this tumor osteolysis murine model allows early measurement of intraosseous tumor growth and bone destruction, as well as correlation between both processes kinetics. This model will help to assess new therapeutic approaches targeting intraosseous tumor growth or tumor/osteoclast crosstalk.