Drug streaming during intra-arterial chemotherapy

Abstract

✓ Treatment of brain tumors by intra-arterial (IA) chemotherapy is occasionally complicated by sites of focal toxicity in the brain and retina. A possible cause of focal toxicity is non-uniform drug delivery due to intravascular drug streaming. To investigate this phenomenon in vivo, the authors examined the distribution of drug delivery after internal carotid artery (ICA) infusion in rhesus monkeys. Carbon-14 (14C)-labeled iodoantipyrine was delivered into the ICA of eight monkeys at slow infusion rates (1% to 2% of ICA flow) or at fast infusion rates (20% of ICA flow) combined with additional techniques to promote mixing with ICA blood. Two monkeys received intravenous (IV) 14C-antipyrine. Uniformity of delivery was assessed by comparing high-to-low ratios of isotope concentration in four brain regions evaluated by quantitative autoradiography. There was striking non-uniformity of drug delivery in the slow IA infusion group, with as much as 13-fold differences in drug concentration in anatomically contiguous areas. The values of high-to-low concentration ratios (mean ± standard deviation) in individual autoradiographic planes were: 1) frontoparietal cortex: slow IA infusion 4.54 ± 2.07, fast IA infusion 1.71 ± 0.31, IV infusion 1.30 ± 0.174; 2) frontoparietal white matter: slow IA infusion 2.94 ± 1.45, fast IA infusion 1.59 ± 0.41, IV infusion 1.34 ± 0.21; 3) temporal cortex: slow IA infusion 5.43 ± 3.57, fast IA infusion 1.69 ± 0.24, IV infusion 1.67 ± 0.25; 4) basal ganglia: slow IA infusion 3.6 ± 2.9, fast IA infusion 1.18 ± 0.10, IV infusion 1.09 ± 0.04. Differences between concentration ratios after slow IA and fast IA infusion are significant (p < 0.01); those between fast IA and IV infusion are not significant. Intra-arterial drug administration at infusion rates analogous to those currently used clinically results in drug streaming with markedly heterogeneous drug deposition in the perfused hemisphere. This may cause suboptimal drug levels in the tumor, and toxic levels at sites within the perfused hemisphere. This effect can be abrogated by techniques that eliminate drug streaming.