Abstract
Abstract Gold nanoparticles are of interest as potential in vivo diagnostic and therapeutic agents, as X-ray contrast agents, drug delivery vehicles and radiation enhancers. The aim of this study was to quantitatively determine their targeting and microlocalization in mouse tumor models after intravenous injection by using micro- CT. Gold nanoparticles (15 nm) were coated with polyethylene glycol and covalently coupled to anti-Her2 antibodies (Herceptin). In vitro, conjugates incubated with Her2+ (BT-474) and Her2- (MCF7) human breast cancer cells showed specific targeted binding with a Her2+ to Her2- gold ratio of 39.4± 2.7:1. Nude mice, simultaneously bearing subcutaneous Her2+ and Her2- human breast tumors in opposite thighs were prepared. Gold nanoparticles alone, conjugated to Herceptin or to a non-specific antibody were compared. After intravenous injection of the gold nanoparticles, gold concentrations were determined by atomic absorption spectroscopy. Microlocalization of gold was carried out by calibrated micro-CT, giving both the radiodensities and gold concentrations in tumor and non-tumor tissue. All gold nanoparticle constructs showed accumulation, predominantly at tumor peripheries. However, the Herceptin-gold nanoparticles showed the best specific uptake in their periphery (15.8± 1.7% injected dose g-1), 1.6-fold higher than Her2- tumors and 22-fold higher than surrounding muscle. Imaging readily enabled detection of small, 1.5-mm-thick tumors. In this pre-clinical study, antibody-targeted 15 nm gold nanoparticles showed preferential uptake in cognate tumors, but even untargeted gold nanoparticles enhanced the visibility of tumor peripheries and enabled detection of millimeter-sized tumors. Micro-CT enabled quantification within various regions of a tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5329A. doi:10.1158/1538-7445.AM2011-5329A
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