Noninvasive bioluminescence imaging of luciferase expressing intracranial U87 xenografts: correlation with magnetic resonance imaging determined tumor volume and longitudinal use in assessing tumor growth and antiangiogenic treatment effect.
OBJECTIVE
Outcome studies in rodent tumor models rely on both histological and noninvasive study end points. Intracranial models require special tools to observe tumor growth over time noninvasively, such as magnetic resonance imaging (MRI), computed tomographic scanning, or cranial window techniques. These techniques share disadvantages in terms of cost, technical expertise required, and overall animal throughput for analysis. In this report, we sought to validate the use of the relatively newer technique of bioluminescence imaging (BLI) of intracranial glioblastoma xenograft growth by comparing it with gadolinium-enhanced MRI.


METHODS
U87MG glioma cell lines genetically engineered to express the firefly luciferase gene were stereotactically injected into nude mice in the left frontal lobe. Weekly BLI and MRI were performed after the inoculation of tumor cells. For BLI, tumor growth was assessed as the peak BLI after systemic injection of luciferin substrate. MRI-based growth curves were created by three-dimensional volumetric reconstruction of axial gadolinium-enhanced MRI data covering the whole brain. In a separate experiment, mice were treated with adenoviruses encoding antiangiogenic soluble vascular endothelial growth factor receptors, and treatment effect was monitored by BLI.


RESULTS
Untreated tumor growth was readily detected and observed over time by serial BLI measurements. Furthermore, tumor-derived light emission was highly correlated with volume of tumor as assessed by MRI. Furthermore, the tested antiangiogenic treatment effect was readily detected using this technique, suggesting the power of the technique for sensitive monitoring of novel therapeutics.


CONCLUSIONS
BLI offers a simple and rapid technique for assessing intracranial glioblastoma growth in rodent models noninvasively, which correlates well with MRI. The speed of the BLI technique can increase experimental throughput, allows for targeted histological analysis in animals showing the greatest treatment effects, and provides new insights into the kinetics of intracranial tumor growth in the setting of different treatments.
Szentirmai
Oszkar
O
Neurosurgical Service, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Baker
Cheryl H
CH
Lin
Ning
N
Szucs
Szofia
S
Takahashi
Masaya
M
Kiryu
Shigeru
S
Kung
Andrew L
AL
Mulligan
Richard C
RC
Carter
Bob S
BS
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000201:enzymology; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005909:Glioblastoma / Q000175:diagnosis* / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D008137:Longitudinal Studies; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D020533:Angiogenesis Inhibitors; D008164:Luminescent Proteins; D049409:Luciferases, Firefly