Drug streaming during intra-arterial chemotherapy

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Intra-arterial (IA) chemotherapy for brain tumors can lead to focal toxicity.
• Intravascular drug streaming is a suspected cause of non-uniform drug delivery.

Purpose of the Study:

• To investigate the phenomenon of intravascular drug streaming in vivo.
• To assess the uniformity of drug delivery following internal carotid artery (ICA) infusion in rhesus monkeys.

Main Methods:

• Carbon-14 labeled iodoantipyrine was infused into the ICA of rhesus monkeys at slow (1-2% of ICA flow) or fast (20% of ICA flow) rates.
• Some fast infusion groups received techniques to enhance blood mixing.
• Intravenous (IV) infusion was used as a control.
• Quantitative autoradiography assessed isotope distribution in brain regions.

Main Results:

• Slow IA infusion resulted in striking non-uniformity of drug delivery, with up to 13-fold concentration differences in adjacent brain areas.
• Fast IA infusion and IV infusion showed significantly more uniform drug distribution compared to slow IA infusion.
• Differences between fast IA and IV infusion groups were not statistically significant.

Conclusions:

• IA chemotherapy at clinically relevant slow infusion rates causes significant drug streaming and heterogeneous drug deposition.
• This heterogeneity may lead to suboptimal tumor drug levels and off-target toxicity.
• Techniques that eliminate drug streaming can abrogate this non-uniformity.