Non-invasive Imaging Correlates with Histological and Molecular Characteristics of an Osteosarcoma Model: Application for Early Detection and Follow-up of MDR Phenotype

Abstract

Background: In an orthotopic rat osteosarcoma model, histological and molecular findings were compared with the results of non-invasive imaging methods to assess disease progression at the primary site, the pattern of metastatic dissemination and the chemoresistance phenotype. Materials and Methods: Primary tumor engraftment, vascularization, growth and metastatic spread were evaluated using ¹⁸FDG tomoscintigraphy. Bone neoformation in the primary tumor and metastasis was determined using ¹⁸FNa confirmed by classical histological studies. Chemoresistance phenotype was assessed by analysis of MDR1 and MRP1 genes expression compared to ^99mTc MIBI imaging. Results: ^99mTc MIBI imaging correlated with the overexpression of the MDR1 and MRP1 genes. ¹⁸FDG, ¹⁸FNa and ^99mTc tomoscintigraphies revealed that the pattern of vascularization, bone neoformation and hematogeneous metastatic dissemination in our animal model mimics its human counterpart. Conclusion: Multimodality, non-invasive imaging is a valid surrogate marker of histological and molecular characteristics in an orthotopic osteosarcoma model in immunocompetent rats; it allows extensive in vivo follow-up of osteosarcoma, including longitudinal analysis of chemoresistance.