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Published on: December 15, 2010
Focused Ultrasound-Enhanced Delivery of Abraxane to Intramedullary Spinal Cord Tumors
Meghana Bhimreddy1, Hasan Slika1, Ritvik R Jillala1
1Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore , Maryland , USA.
Background And Objectives:
Chemotherapeutic drug delivery to intramedullary spinal cord tumors (IMSCTs) is restricted by the blood-spinal cord barrier. Focused ultrasound (FUS), however, can transiently disrupt the blood-spinal cord barrier. Therefore, this study investigates the feasibility of using FUS-enhanced Abraxane (albumin-bound paclitaxel) delivery to improve the treatment of IMSCTs using a rodent model.
Methods:
Twenty-eight F344 rats received an intramedullary injection of 100 000 luciferase-tagged 9L gliosarcoma cells. Rats were classified into 4 cohorts: no-treatment, FUS, Abraxane, and FUS-enhanced Abraxane delivery. Treatments were administered on days 7, 14, and 21. Tumor burden was assessed weekly using bioluminescence-based imaging. Twice a week, nociceptive thresholds were assessed using the Von Frey Filament test, and motor function was assessed using the Basso-Beattie-Bresnahan locomotor scale.
Results:
The FUS-enhanced Abraxane delivery cohort had significantly decreased tumor burden ([1.52 ± 0.69] × 106 photons/s) compared with the no-treatment ([9.03 ± 5.13] × 106 photons/s), FUS-only ([8.25 ± 1.58] × 106 photons/s) and Abraxane-only ([4.19 ± 1.91] × 106 photons/s) groups (day 18, P < .0001). Although all rodents initially demonstrated motor decline, the FUS-enhanced Abraxane group had complete return-to-baseline motor scores (21.0) by day 27, whereas the no-treatment (8.3 ± 1.5), FUS-only (6.0 ± 1.4), and Abraxane-only (16.3 ± 1.3) cohorts maintained decreased Basso, Beattie, and Bresnahan scale scores to day 48. Similarly, while all animals demonstrated initial hypersensitivity to pain, only the FUS-enhanced Abraxane group returned to baseline pain response by day 48 (17.4 ± 6.1 g) when compared with the no-treatment (7.0 ± 6.2 g), FUS-only (5.0 ± 1.4 g), and Abraxane-only (11.2 ± 7.5 g) cohorts.
Conclusion:
FUS-enhanced Abraxane delivery significantly reduced IMSCT tumor burden and improved neurological recovery over intravenous administration alone. Therefore, FUS-mediated chemotherapeutic drug delivery may represent a noninvasive, clinically relevant, and effective treatment paradigm for intramedullary pathologies.
