Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease.
The development of novel anti-cancer strategies requires more sensitive and less invasive methods to detect and monitor in vivo minimal residual disease in cancer models. Bone marrow metastases are indirectly detected by radiography as osteolytic and/or osteosclerotic lesions. Marrow micrometastases elude radiographic detection and, therefore, more sensitive methods are needed for their direct identification. Injection of cancer cells into the left cardiac ventricle of mice closely mimics micrometastatic spread. When luciferase-transfected cells are used, whole-body bioluminescent reporter imaging can detect microscopic bone marrow metastases of approximately 0.5 mm(3) volume, a size below the limit in which tumors need to induce angiogenesis for further growth. This sensitivity translates into early detection of intramedullary tumor growth, preceding the appearance of a radiologically evident osteolysis by approximately 2 weeks. Bioluminescent reporter imaging also enables continuous monitoring in the same animal of growth kinetics for each metastatic site and guides end-point analyses specifically to the bones affected by metastatic growth. This model will accelerate the understanding of the molecular events in metastasis and the evaluation of novel therapies aiming at repressing initial stages of metastatic growth.
Wetterwald
Antoinette
A
Department of Clinical Research, University of Bern, Inselspital, Bern, Switzerland.
van der Pluijm
Gabri
G
Que
Ivo
I
Sijmons
Bianca
B
Buijs
Jeroen
J
Karperien
Marcel
M
Löwik
Clemens W G M
CW
Gautschi
Elsbeth
E
Thalmann
George N
GN
Cecchini
Marco G
MG
D000818:Animals; D019046:Bone Marrow Neoplasms / Q000473:pathology / Q000556:secondary*; D004195:Disease Models, Animal; D005260:Female; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D018365:Neoplasm, Residual / Q000473:pathology*