Rat model of metastatic breast cancer monitored by MRI at 3 tesla and bioluminescence imaging with histological correlation.
BACKGROUND
Establishing a large rodent model of brain metastasis that can be monitored using clinically relevant magnetic resonance imaging (MRI) techniques is challenging. Non-invasive imaging of brain metastasis in mice usually requires high field strength MR units and long imaging acquisition times. Using the brain seeking MDA-MB-231BR transfected with luciferase gene, a metastatic breast cancer brain tumor model was investigated in the nude rat. Serial MRI and bioluminescence imaging (BLI) was performed and findings were correlated with histology. Results demonstrated the utility of multimodality imaging in identifying unexpected sights of metastasis and monitoring the progression of disease in the nude rat.


METHODS
Brain seeking breast cancer cells MDA-MB-231BR transfected with firefly luciferase (231BRL) were labeled with ferumoxides-protamine sulfate (FEPro) and 1-3 x 106 cells were intracardiac (IC) injected. MRI and BLI were performed up to 4 weeks to monitor the early breast cancer cell infiltration into the brain and formation of metastases. Rats were euthanized at different time points and the imaging findings were correlated with histological analysis to validate the presence of metastases in tissues.


RESULTS
Early metastasis of the FEPro labeled 231BRL were demonstrated on T2*-weighted MRI and BLI within 1 week post IC injection of cells. Micro-metastatic tumors were detected in the brain on T2-weighted MRI as early as 2 weeks post-injection in greater than 85% of rats. Unexpected skeletal metastases from the 231BRL cells were demonstrated and validated by multimodal imaging. Brain metastases were clearly visible on T2 weighted MRI by 3-4 weeks post infusion of 231BRL cells, however BLI did not demonstrate photon flux activity originating from the brain in all animals due to scattering of the photons from tumors.


CONCLUSIONS
A model of metastatic breast cancer in the nude rat was successfully developed and evaluated using multimodal imaging including MRI and BLI providing the ability to study the temporal and spatial distribution of metastases in the brain and skeleton.
Song
Ho-Taek
HT
Frank Laboratory, Radiology and Imaging Sciences Clinical Center, National Institute of Health, Bethesda, MD, USA. hotsong@yuhs.ac
Jordan
Elaine K
EK
Lewis
Bobbi K
BK
Liu
Wei
W
Ganjei
Justin
J
Klaunberg
Brenda
B
Despres
Daryl
D
Palmieri
Diane
D
Frank
Joseph A
JA
D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology; D001932:Brain Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D011479:Protamines / Q000737:chemistry / Q000378:metabolism; D051381:Rats
D003911:Dextrans; D058185:Magnetite Nanoparticles; D011479:Protamines; D049409:Luciferases, Firefly; C065507:ferumoxides; D052203:Ferrosoferric Oxide