International Brain Tumour Awareness Week
Saturday, 24th October to Saturday, 31st October 2020
Intra-arterial (IA) chemotherapy for brain tumours is administered through a catheter inserted into the carotid or vertebral artery. The drugs then travel through capillary networks of the bloodstream and, eventually, into brain tissue. Studies to date have shown that the intra-arterial route is significantly more effective for drug delivery to the brain than the intravenous route (also via the bloodstream).
The commonest method of intra-arterial therapy in the brain is in the treatment of retinoblastoma. The catheter is placed in the ophthalmic artery, which is an end artery supplying the eye. This offers excellent access for drug infusions to the site of the tumour in the retina.
To target treatment more specifically to a brain tumour, chemotherapy can be infused into the main tumour-supplying arteries rather than into the carotid or vertebral arteries. This is called super-selective intra-arterial chemotherapy. It is safe and technically feasible due to advancements in microcatheter design and imaging systems that facilitate navigation through the delicate vessels within the brain.
For effective IA drug delivery, drugs have to be rapidly, and preferably irreversibly, taken up into the brain during their first pass through the tissue circulation. This first pass lasts between 1 and 10 seconds in the brain. This needs to be taken into consideration during drug design to ensure that a high number of drug molecules are retained in the brain and can reach the tumour. Researchers are currently trying to improve the effectiveness of IA by designing drugs that are very small or that can attach to the abundant fat molecules present in the brain. They are also investigating the use of drugs that are designed to activate the patient’s own immune system.
Reduction of blood flow during IA administration can lead to better targeting of drugs to the tumour site. Furthermore, disruption of the BBB using a sugary alcohol called mannitol is often used to improve IA drug delivery. Only mannitol has been approved for use in this regard in a clinical setting, although alternatives such as bradykinin analogues, focused ultrasound and cell-penetrating peptides (fragments of protein) are being investigated.
The recent addition of Magnetic Resonance Imaging (MRI) guidance to IA administration has enabled more precise BBB opening. Furthermore, new optical technologies are helping us to understand the complex movement of drugs within the brain and body when delivered by IA, which may lead to improved clinical effectiveness.
Video from Interventional Neuroradiology on YouTube.