Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model

Jon A. Schwartz; Anil M. Shetty; Roger E. Price; R. Jason Stafford; James C. Wang; Rajesh K. Uthamanthil; Kevin Pham; Roger J. McNichols; Chris L. Coleman M.D.; J. Donald Payne

doi:10.1117/12.808334

23 February 2009 Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model

Jon A. Schwartz, Anil M. Shetty, Roger E. Price, R. Jason Stafford, James C. Wang, Rajesh K. Uthamanthil, Kevin Pham, Roger J. McNichols, Chris L. Coleman M.D., J. Donald Payne

Author Affiliations +

Proceedings Volume 7161, Photonic Therapeutics and Diagnostics V; 716130 (2009) https://doi.org/10.1117/12.808334
Event: SPIE BiOS, 2009, San Jose, California, United States

Abstract

We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8±4.1ºC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6±1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

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Jon A. Schwartz, Anil M. Shetty, Roger E. Price, R. Jason Stafford, James C. Wang, Rajesh K. Uthamanthil, Kevin Pham, Roger J. McNichols, Chris L. Coleman M.D., and J. Donald Payne "Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model", Proc. SPIE 7161, Photonic Therapeutics and Diagnostics V, 716130 (23 February 2009); https://doi.org/10.1117/12.808334

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