MR temperature imaging of nanoshell mediated laser ablation.

ABSTRACT

Minimally invasive thermal therapy using high-power diode lasers is an active area of clinical research. Gold nanoshells (AuNS) can be tuned to absorb light in the range used for laser ablation and may facilitate more conformal tumor heating and sparing of normal tissue via enhanced tumor specific heating. This concept was investigated in a xenograft model of prostate cancer (PC-3) using MR temperature imaging (MRTI) in a 1.5T scanner to characterize the spatiotemporal temperature distribution resulting from nanoparticle mediated heating. Tumors with and without intravenously injected AuNS were exposed to an external laser tuned to 808 nm for 180 sec at 4 W/cm(2) under real-time monitoring with proton resonance frequency shift based MRTI. Microscopy indicated that these nanoparticles (140-150 nm) accumulated passively in the tumor and remained close to the tumor microvasculature. MRTI measured a statistically significant (p < 0.001) increase in maximum temperature in the tumor cortex (mean = 21 ± 7°C) in +AuNS tumors versus control tumors. Analysis of the temperature maps helped demonstrate that the overall distribution of temperature within +AuNS tumors was demonstrably higher versus control, and resulted in damage visible on histopathology. This research demonstrates that passive uptake of intravenously injected AuNS in PC-3 xenografts converts the tumor vasculature into a potent heating source for nanoparticle mediated ablation at power levels which do not generate significant damage in normal tissue. When used in conjunction with MRTI, this has implications for development and validation of more conformal delivery of therapy for interstitial laser ablations.