Abstract
For over six decades intra-arterial (IA) drugs have been sporadically used for the treatment of lethal brain diseases. In recent years considerable advance has been made in the IA treatment of retinoblastomas, liver and locally invasive breast cancers, but relatively little progress has been made in the treatment of brain cancers. High resting blood flow and the presence of the blood-brain barrier (BBB), makes IA delivery to the brain tissue far more challenging, compared to other organs. The lack of advance in the field is also partly due to the inability to understand the complex pharmacokinetics of IA drugs as it is difficult to track drug concentrations in sub-second time frame by conventional chemical methods. The advances in optical imaging now provide unprecedented insights into the pharmacokinetics of IA drug and optical tracer delivery. Novel delivery methods, improved IA drug formulations, and optical pharmacokinetics, present us with untested paradigms in pharmacology that could lead to new therapeutic interventions for brain cancers and stroke. The object of this review is to bring into focus the current practice, problems, and the potential of IA drug delivery for treating brain diseases. A concerted effort is needed at basic sciences (pharmacology and drug imaging), and translational (drug delivery techniques and protocol development) levels by the interventional neuroradiology community to advance the field.
Highlights
Quick Response Code: Website: www.jnaccjournal.org resting cerebral blood flow and the presence of the blood brain barrier (BBB), makes IA drug delivery to the brain far more challenging compared to other organs
The failure in treating brain diseases with IA drugs is in part due to a continuing lack of understanding of IA pharmacokinetics, unavailability of convenient high‐speed drug concentration measurement methods, poor rationalisation of drug injection protocols and the use of drugs and formulations without adequate pharmacokinetic justifications –many of which were never developed for IA use in the first place
Optical methods, such as diffuse reflectance spectroscopy,[96,97,98,99] multi‐spectral and hyperspectral imaging, spatial frequency domain imaging (SFDI),[100,101,102] confocal microscopy and spectroscopy, and even optical coherence tomography provide us with novel pharmacokinetic tools
Summary
For over six decades intra‐arterial (IA) drugs have been proposed for the treatment of lethal brain diseases.[1,2,3,4] Recent reports of super‐selective intraarterial (IA) injections of bevacizumab for treating human gliomas have brought IA drug delivery back into focus.[5,6,7,8] In contrast to treatment of brain cancers the interest in IA chemotherapy for treating liver and breast cancers has considerably increased in the last three decades [Figure 1].[9,10] Major advances have been made in using IA chemotherapy of retinoblastomas to avoid surgical removal and improve function.[11,12,13,14,15] High
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