Journal
STEREOTACTIC AND FUNCTIONAL NEUROSURGERY
Volume 89, Issue 3, Pages 141-151Publisher
KARGER
DOI: 10.1159/000323544
Keywords
Convection-enhanced delivery; Interventional MRI; Gene therapy; Drug delivery
Categories
Funding
- NIH [P01 CA118816, F32 NS064692]
- NATIONAL CANCER INSTITUTE [P01CA118816] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [F32NS064692] Funding Source: NIH RePORTER
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Background/Aims: A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods: Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results: The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R-2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions: This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion. Copyright (C) 2011 S. Karger AG, Basel
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