Convection Enhanced Delivery (CED)

Numerous strategies have been developed and studied to facilitate delivery of therapeutic agents to the brain. The most popular approaches have involved systemic administration of agents orally or intravenously. However, many systemically delivered drugs have a very limited ability to penetrate the blood-brain-barrier, which significantly limits their efficacy.

Convection Enhanced Delivery (CED) is a therapeutic strategy that was developed to facilitate targeted delivery of pharmaceuticals to the brain. The CED procedure involves a minimally invasive surgical exposure of the brain, followed by placement of small diameter catheters directly into the brain tumor. Subsequently, infusion of therapeutics into the tumor occurs over several hours to saturate the target tissue. As this approach effectively bypasses the blood-brain-barrier, it allows for delivery of macromolecular drugs that would not normally enter the brain to effectively reach high concentrations within brain tumor tissue. In order to reach similar concentrations as those achieved with CED, systemically administered conventional chemotherapeutic agents would need to be given at doses that would result in significant toxicity. Thus, an additional benefit of CED is that it simultaneously limits exposure of the remainder of the body to the therapeutic agent and thus minimizes systemic drug- related adverse effects

As CED holds great promise as a therapeutic platform to effectively deliver drugs to focal regions of the brain, it is being investigated extensively in the biomedical and neuroscience communities. CED has been performed safely in dogs and humans with spontaneous brain tumors. Recent studies have also shown that monitoring of CED treatments with MRI is feasible, essential to confirm adequate drug delivery to the tumor, and helpful to clinicians by allowing for necessary modifications to the procedure during the treatment based on real-time feedback.

Schematic of the CED procedure used in the clinical trial. The dog is anesthetized and a catheter guide pedestal is surgically implanted into the skull. This facilitates accurate and secure placement of the catheter in a direct trajectory to the brain tumor for the infusion. The experimental drug cocktail is slowly infused into the tumor and monitored with MRI. Following completion of the infusion, the catheter is removed and the dog is recovered from anesthesia.
Time lapsed MRI depicting a CED infusion into the subcortical white matter of the canine brain. In this case, the therapeutic drug is tagged to a gadolinium-based contrast agent, so that the volume of distribution of the infusate is visible on the MRI as a “white plume” against the dark background of the brain, which enlarges over time. Monitoring CED treatments in real time with this technique allows clinicians to confirm that the target region was accurately infused.