title: Feasibility study of particle-assisted laser ablation of brain tumors in orthotopic canine model.
abstract: We report on a pilot study showing 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 photothermal ablation of canine transmissible venereal tumor (cTVT) in a canine brain model. cTVT fragments grown in severe combined immunodeficient mice were successfully inoculated in the parietal lobe of immunosuppressed, mixed-breed hound dogs. A single dose of near-IR (NIR)-absorbing, 150-nm nanoshells was infused i.v. 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 neovasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, NIR 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 +/- 4.1 degrees C. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sublethal temperatures of 48.6 +/- 1.1 degrees C. 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. Postmortem histopathology of treated brain sections showed the effectiveness and selectivity of the nanoshell-assisted thermal ablation.
authors.affiliation: Nanospectra Biosciences, Inc, Houston, Texas 77054, USA.
authors.forename: Jon A
authors.initials: JA
authors.lastname: Schwartz
authors.forename: Anil M
authors.initials: AM
authors.lastname: Shetty
authors.forename: Roger E
authors.initials: RE
authors.lastname: Price
authors.forename: R Jason
authors.initials: RJ
authors.lastname: Stafford
authors.forename: James C
authors.initials: JC
authors.lastname: Wang
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Uthamanthil
authors.forename: Kevin
authors.initials: K
authors.lastname: Pham
authors.forename: Roger J
authors.initials: RJ
authors.lastname: McNichols
authors.forename: Chris L
authors.initials: CL
authors.lastname: Coleman
authors.forename: J Donald
authors.initials: JD
authors.lastname: Payne
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000453:epidemiology / Q000601:surgery*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D015994:Incidence; D007259:Infrared Rays; D053685:Laser Therapy / Q000379:methods*; D008297:Male; D049329:Nanostructures; D014481:United States / Q000453:epidemiology; D014685:Venereal Tumors, Veterinary / Q000601:surgery