chapter  10
Radiolabeled Gold Nanoshells for in vivo Imaging: Example of Methodology for Initial Evaluation of Biodistribution of a Novel Nanoparticle
Pages 12

Southern University, Houston, Texas, USA b Department of Radiology, University of Texas Health Science Center at San Antonio (UTHSC-San Antonio), San Antonio, Texas, USA c MPI Research, Inc., Mattawan, Michigan, USA xieh@tsu.edu

10.1 INTRODUCTIONOne of the most promising recent advances in cancer treatment is thermal ablation, which provides a minimally invasive or noninvasive cancer therapy technique that rapidly kills cancer cells by heat. Cancer cell death is related to both the temperature and the time period of thermal exposure. Previously investigated thermal therapies have employed a variety of heat sources, including radiofrequency, focused ultrasound, and microwaves [6]. The advantages of thermal ablation include minimal or noninvasive application, relatively simple to perform, and the potential of treating embedded tumors in vital regions where surgical resection is not feasible. However, simple heating techniques have trouble discriminating between tumors and surrounding healthy tissues, and often heat intervening tissue between the source and the target site. Nanoshell-based photothermal ablation, a laser-induced thermal therapy that utilizes special nanoshell optical properties, offers advantages over Nanoimaging Edited by Beth Goins and William Phillips Copyright © 2011 by Pan Stanford Publishing Pte. Ltd. www.panstanford.com

traditional thermal therapies, and this approach has obtained much attention in the past several years. Nanoparticles have been intensively studied and broadly utilized for biological applications, such as molecular imaging, molecular diagnosis, and targeted therapy. Among newly developed nanoparticles, gold nanoshells are of special interest for cancer treatment because of their unique size, composition, and physical and optical properties. Nanoshells are spherical nanoparticles consisting of a dielectric core and a metal shell, where the plasmon resonance frequency is determined by the relative size of the core and the metal shell layer [12]. By adjusting the relative core and shell thicknesses, nanoshells can be fabricated that will absorb or scatter light across the visible and near-infrared regions (NIR: 700-1300 nm) of the electromagnetic spectrum, where optical transmission through tissue is optimal. Silica core gold nanoshells are made of biocompatible materials, and their surface can be modified with “stealthing” polymers such as polyethylene glycol (PEG) to further improve their biocompatibility and prolong their circulation in vivo. They can also be manufactured with size ranges (60-400 nm) that can accumulate in tumors via the enhanced permeability and retention (EPR) effect, which is attributed to the leaky nature of tumor vessels [10]. Nanoshell-based photothermal ablation that utilizes special nanoshell optical properties and NIR laser has been demonstrated to be effective in the elimination of solid tumors in animal models [3, 11]. O’Neal et al. applied PEG-coated nanoshells (~130 nm diameter) with peak optical absorption in the NIR to treat tumor-bearing mice. Following intravenous administration, tumors were then illuminated with a diode laser (808 nm, 4 W/cm2, 3 min). All such treated tumors were effectively abated, and treated mice appeared healthy and tumor free even after 90 days.