In Vivo Bioluminescence Tomography for Monitoring Breast Tumor Growth and Metastatic Spreading: Comparative Study and Mathematical Modeling.
This study aimed at evaluating the reliability and precision of Diffuse Luminescent Imaging Tomography (DLIT) for monitoring primary tumor and metastatic spreading in breast cancer mice, and to develop a biomathematical model to describe the collected data. Using orthotopic mammary fat pad model of breast cancer (MDAMB231-Luc) in mice, we monitored tumor and metastatic spreading by three-dimensional (3D) bioluminescence and cross-validated it with standard bioluminescence imaging, caliper measurement and necropsy examination. DLIT imaging proved to be reproducible and reliable throughout time. It was possible to discriminate secondary lesions from the main breast cancer, without removing the primary tumor. Preferential metastatic sites were lungs, peritoneum and lymph nodes. Necropsy examinations confirmed DLIT measurements. Marked differences in growth profiles were observed, with an overestimation of the exponential phase when using a caliper as compared with bioluminescence. Our mathematical model taking into account the balance between living and necrotic cells proved to be able to reproduce the experimental data obtained with a caliper or DLIT imaging, because it could discriminate proliferative living cells from a more composite mass consisting of tumor cells, necrotic cell, or inflammatory tissues. DLIT imaging combined with mathematical modeling could be a powerful and informative tool in experimental oncology.
Pharmacokinectics Laboratory, SMARTc Unit, Inserm S_911 CrO2, Aix-Marseille Univ, Marseille, France.|Pharmacology &Drug Development Group, Cancer Research UK Cambridge Research Institute, and Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
Séverine
S
Mollard
Pharmacokinectics Laboratory, SMARTc Unit, Inserm S_911 CrO2, Aix-Marseille Univ, Marseille, France.
Raphaelle
R
Fanciullino
Pharmacokinectics Laboratory, SMARTc Unit, Inserm S_911 CrO2, Aix-Marseille Univ, Marseille, France.
Sarah
S
Giacometti
Pharmacokinectics Laboratory, SMARTc Unit, Inserm S_911 CrO2, Aix-Marseille Univ, Marseille, France.
Cindy
C
Serdjebi
MONC Team INRIA, Bordeaux France.
Sebastien
S
Benzekry
Pharmacokinectics Laboratory, SMARTc Unit, Inserm S_911 CrO2, Aix-Marseille Univ, Marseille, France.
Joseph
J
Ciccolini
D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D045744:Cell Line, Tumor; D005260:Female; D064593:Heterografts; D006801:Humans; D021621:Imaging, Three-Dimensional; D008163:Luminescent Measurements; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000556:secondary*; D051379:Mice; D008954:Models, Biological; D015203:Reproducibility of Results; D041622:Tomography, Optical / Q000379:methods