Brain tumors are the second leading cause of cancer-related deaths in children and fourth in middle-aged man. Malignant gliomas remain uniformly fatal underscoring the urgent need for new, more effective treatments. More effective therapies coupled with improved imaging information would provide important opportunities to improve care and individualize treatments. The central hypothesis of this SBIR is that a new formulation of BCNU in absolute ethanol (DTI-015) can be administered locafly to treat experimental gliomas and that the spatial delivery of this therapy can be monitored using MRI for subsequent correlation with therapeutic outcome. The regional distribution of vascular effects following DTI-015 injection in experimental animals will be mapped using the perfusion tracer HMPAO. The regional distribution of DTI-015 may be observed with the use of MR through: 1) local trapping of infused intravascular MR contrast in the affected vascular bed; 2) arterial spin-labeling perfusion imaging; 3) bolus intravascular contrast MR perfusion imaging or 4) diffusion-weighted MRI. The MR-observable parameter that can be used as a surrogate marker for detecting drug delivery will be determined. These results are anticipated to provide the foundation for using SPECT and MR in DTI-015 clinical trials.
Current treatments for malignant brain tumors are very ineffective and improvements in mean lifespan has not changed for over 20 years for this patient population. A therapeutic approach proven to extend survival would have a tremendous impact and be a commercially viable product.
