MR guided focused ultrasound of the brain and targeted delivery of therapeutics

Date: 03/28/2012
Time: 10:30 am
Location: 306 Egan
Speaker: Rivka R. Colen, M.D., Brigham and Women’s Hospital, Dept. of Radiology

Targeted drug delivery using MRI-guided focused ultrasound (MRgFUS) can be expected to revolutionize CNS disease treatment and emerge as both a viable alternative and adjunct to current therapy. The ability of MRgFUS to reversibly disrupt the blood brain barrier (BBB), thereby increasing permeability to formerly non-penetrating compounds, can potentially transform and replace current non-selective drug delivery methods that cause systemic toxicity and enable the delivery of targeted chemotherapy drugs into the region of interest that would otherwise not enter the desired site due to almost complete impermeable tight junctions at the BBB. Despite advancements in Glioblastoma multiforme (GBM) treatment, delivery of chemotherapy across the BBB remains a challenge and prognosis remains dismal; surgery, radiation, and concurrent temozolomide (TMZ) continue to remain the current standard of care for the treatment of GBM. Although some drugs demonstrate some permeability through the BBB, their concentration remains markedly higher in the plasma relative to the brain parenchyma. This relative impermeability might inhibit and, thereby, preclude these drugs from reaching their optimal therapeutic and clinical effect. An increase in drug delivery into the brain after BBB disruption (BBBD) can be anticipated to increase its therapeutic effect optimizing it to reach its full clinical potential. Recent studies performed at our institution demonstrated the ability of MRgFUS to produce selective, targeted,reversible disruption of the BBB and, subsequently, the ability of large molecular drugs, such as Herceptin and doxorubicin, to cross the BBB after sonication. We are currently researching this using a high impact, clinically proven, already FDA-approved chemotherapy drug, TMZ and Bortezomib. Targeted drug delivery using MRgFUS has the potential to cause a radical shift in the brain tumor treatment paradigm and create new opportunities for drug development and allowing new uses of currently available drug therapies. It can be expected that demonstration of an increased delivery of therapeutics to the targeted and perilesional tissues will result in an increase in survival times and have a large clinical impact and significantly change the current standard of care.