| Projects > 2011 > Joe Benci

Quantitative Analyses of an Orthotopic Model of GBM: Evaluation of the Bioluminescence to Tumor Volume Relationship, Radiation-Induced BBB Disruption, and Enhancement of Nanocarrier Extravasation after Radiation

Joe Benci
mentored by Dr. Jay Dorsey and Dr. Gary Kao

Hypotheses
In a mouse model of GBM, the volume of intercranial tumors determined by MRI would correlate well with the BLI data from the IVIS imaging system. Secondly, a commercially availabel infrared dye, IRDye 800CW PEG contrast agent would be an effective indicator of blood brain barrier (BBB) and blood tumor barrier (BTB) disruption by ionizing radiation in vivo. If so, this would allow for tracking the short and long-term effects of BBB and BTB disruption in response to ionizing radiation. Third, that irradiation of an orthotopic GBM tumor would lead to an increased tumor uptake of novel worm-shaped nanocarriers which were visualized and quantified by loading with a fluorescent dye encapsulation.







Techniques
:: Stereotaxic Intercranial Injections.
:: Small Animal Magnetic Responance Imaging (MRI).
:: Bioluminescent Imaging (BLI).
:: Fluorescent Imaging.
:: Amira.
:: Cell Culture.

Conclusions
:: The signal from BLI was a very accurate predictor of tumor volume up to a certain signal threshold at which the bioluminescence peaked but volumes continued to increase (likely due to a variety of factors including necrosis).
:: Increased extravasation of the IRDye was present in the brains of irradiated mice which suggested blood brain barrier disruption but more expierments are needed to confirm this hypothesis.
:: The worm-shaped nanocarrier was able to more effectively permeate the tumor tissue after irradiation and was retained there longer, suggesting this method of drug delivery, given in conjunction with ionizing radiation could be an effective method for treating glioblastoma in the clinic in the future.