Relevance of the POS-1 Orthotopic Model as an “Imaging Model” for In Vivo and Simultaneous Monitoring of Tumor Proliferation and Bone Remodeling in Osteosarcoma

Abstract

Introduction:

Osteosarcoma (OS) management requires a better understanding of tumor/bone interactions in vivo during disease progression. Using [¹⁸F]-FDG and [^99mTc]-HMDP imaging, we assessed a methodology for an in vivo quantitative characterization of an orthotopic model of osteolytic OS on the basis of (1) tumor proliferation, (2) tumor and bone metabolic activities, and (3) bone remodeling.

Methods:

POS-1 tumor bearing mice were monitored in vivo over a 26-day period, with tumor and bone metabolic volumes (TMV and BMV, respectively) being determined from [¹⁸F]-FDG, bone remodeling from [^99mTc]-HMDP, and tumoral volume from micro- computed tomography scans.

Results:

From day 10, [¹⁸F]-FDG strongly accumulated within POS-1 tumor, with a tumor/muscle ratio of 3.7±0.8. TMV and BMV increased as pathology progressed: TMV increased at early stage of pathology (from 56%) whereas BMV strongly increased (from 113%) during late stage. From [^99mTc]-HMDP imaging, bone remodeling features were evidenced within the distal region of tibia bearing the tumor, with a mean scintigraphic ratio of 1.36±0.11 at day 12, that reached value of 2.53±0.19 at day 26.

Conclusions:

Our results validated the POS-1 orthotopic model as “OS imaging model,” that could serve for evaluating in vivo therapies targeting tumor proliferation and/or bone remodeling in OS.