Quantification of Gold Nanoparticles in Mouse Tissues Using Neutron Activation Analysis
Russell P. Watson,1 Rachel S. Popelka-Filcoff,1 Gabriela Kramer-Marek,2 Elizabeth A. Mackey,1, Rabia O. Spatz,1 and Jacek Capala2
1Analytical Chemistry Division, NIST, Gaithersburg, Maryland
2National Cancer Institute, NIH, Bethesda, Maryland
In cancer treatment, gold nanoparticles show promise as X-ray contrast agents for diagnostic imaging and in the eradication of tumors through photothermal ablation, X-ray dose enhancement, and radiation therapy. We are developing potential gold nanoparticle-based radiopharmaceuticals in which the nearly mono-energetic 412 keV gamma radiation of 198Au is used for single photon emission computed tomographic (SPECT) imaging while the same gamma radiation and the accompanying beta radiation are used to destroy cancer cells. To minimize damage to healthy cells and maximize tumor necrosis, the gold-containing chemotherapeutics must be sequestered in the tumors. For the targeted delivery of the gold nanoparticles, we have attached synthetic biomolecules called Affibodies,® which are polypeptides approximately twenty times less massive than commonly used antibodies. The Affibodies employed in this work selectively bind the human epidermal growth factor receptor-2 (HER2), which is overexpressed in certain breast and lung tumors. Because the efficacy of the targeted delivery of the Affibody-functionalized gold nanoparticles must be assessed by studying their biological distribution, we are developing instrumental neutron activation analysis (INAA) protocols that can be applied to these pharmacokinetic studies. INAA is advantageous because of its high sensitivity for gold, its capacity for high-throughput analyses, and the obviation of chemical manipulation of the samples.
At the National Cancer Institute, mice were injected with Affibody-functionalized gold nanoparticle solutions and sacrificed at specific time periods after this injection. Eleven tissues, including breast tumor, were removed and transferred to NIST for analysis. Each tissue was irradiated in the NBS reactor at the NIST Center for Neutron Research (NCNR) and their gold contents measured using gamma-ray spectrometry. Our results to date indicate that the majority of the gold remaining at each time period is accumulated in the liver and kidney tissue. In addition, the blood and lungs retain higher concentrations of gold than do the tumors. Conversely, the gold concentrations in the spleen, heart, pancreas, intestine, and bone tissues are lower than those in the tumors at all time periods. Further studies to quantify trends in accumulation are on-going, including investigations of the effects of nanoparticle size and coating, and nature of the attached Affibody on the biodistribution of the nanoparticles.