skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep15673· OSTI ID:1239142
 [1];  [2];  [2];  [2];  [1]
  1. Brown Univ., Providence, RI (United States)
  2. Rhode Island Hospital and Warren Alpert Medical School of Brown Univ., Providence, RI (United States)

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. As a result, the enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

Research Organization:
Brown Univ., Providence, RI (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
FG02-08ER15937
OSTI ID:
1239142
Journal Information:
Scientific Reports, Vol. 5; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 6 works
Citation information provided by
Web of Science

References (54)

Functional imaging techniques in hepatocellular carcinoma journal March 2012
Global cancer statistics journal February 2011
Recent advances in the natural history of hepatocellular carcinoma journal May 2008
Diagnostic Imaging of Hepatocellular Carcinoma: Recent Progress journal January 2011
Ultrasonography, Computed Tomography and Magnetic Resonance Imaging of Hepatocellular Carcinoma: Toward Improved Treatment Decisions journal January 2011
Accuracy of Ultrasonography, Spiral CT, Magnetic Resonance, and Alpha-Fetoprotein in Diagnosing Hepatocellular Carcinoma: A Systematic Review. CME journal March 2006
New aspects of diagnosis and therapy of hepatocellular carcinoma journal June 2006
Recent Advances in Imaging Hepatocellular Carcinoma: Diagnosis, Staging and Response Assessment journal January 2004
Imaging of hepatocellular carcinoma journal August 1999
Magnetic resonance imaging of hepatocellular carcinoma journal November 2004
Spatial Harmonic Imaging of X-ray Scattering—Initial Results journal August 2008
Fourier X-ray Scattering Radiography Yields Bone Structural Information journal June 2009
Selective imaging of nano-particle contrast agents by a single-shot x-ray diffraction technique journal January 2010
Nanomaterials for X-ray Imaging: Gold Nanoparticle Enhancement of X-ray Scatter Imaging of Hepatocellular Carcinoma journal July 2011
X-ray spatial harmonic imaging of phase objects journal January 2011
X-ray spatial frequency heterodyne imaging journal February 2012
Hard-X-ray dark-field imaging using a grating interferometer journal January 2008
Hard X-ray dark-field imaging with incoherent sample illumination journal January 2014
On the origin of visibility contrast in x-ray Talbot interferometry journal January 2010
Gold nanoparticles: a new X-ray contrast agent journal March 2006
Antibiofouling Polymer-Coated Gold Nanoparticles as a Contrast Agent for in Vivo X-ray Computed Tomography Imaging journal June 2007
X-ray computed tomography contrast agents prepared by seeded growth of gold nanoparticles in PEGylated dendrimer journal May 2010
Targeted Gold Nanoparticles Enable Molecular CT Imaging of Cancer journal December 2008
A highly sensitive x-ray imaging modality for hepatocellular carcinoma detection in vitro journal January 2015
X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents journal January 2014
Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles journal May 2008
In Pursuit of Zero: Polymer Brushes that Resist the Adsorption of Proteins journal June 2009
Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection journal September 2010
Quantitative Evaluation of Cellular Uptake and Trafficking of Plain and Polyethylene Glycol-Coated Gold Nanoparticles journal July 2010
Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy journal October 2009
Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody journal July 2007
Biotin−Streptavidin-Induced Aggregation of Gold Nanorods:  Tuning Rod−Rod Orientation journal November 2005
Engineering of Hetero-Functional Gold Nanorods for the in vivo Molecular Targeting of Breast Cancer Cells journal January 2009
Cyclodextrin-covered gold nanoparticles for targeted delivery of an anti-cancer drug journal January 2009
Design and Characterization of HER-2-Targeted Gold Nanoparticles for Enhanced X-radiation Treatment of Locally Advanced Breast Cancer journal September 2010
Rapid Uptake of Gold Nanorods by Primary Human Blood Phagocytes and Immunomodulatory Effects of Surface Chemistry journal May 2010
Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake journal April 2002
Differentiation and function of Kupffer cells journal March 2004
Role of Kupffer cells in host defense and liver disease journal December 2006
Role of the Kupffer Cell in Mediating Hepatic Toxicity and Carcinogenesis journal November 2006
Kupffer cells are central in the removal of nanoparticles from the organism journal January 2007
A conjugate of 5-fluorouridine-poly(L-lysine) and an antibody reactive with human colon carcinoma journal July 1990
Radioimmunolocation of Hepatic and Pulmonary Metastasis of Human Colon Adenocarcinoma journal May 1989
Antibody-directed therapy for human hepatocellular carcinoma journal November 2004
Prognostic value of aspartyl (asparaginyl)-β-hydroxylase/humbug expression in non–small cell lung carcinoma journal May 2009
Colloidal Gold: A Novel Nanoparticle Vector for Tumor Directed Drug Delivery journal January 2004
Gold Nanoparticles as a Versatile Platform for Optimizing Physicochemical Parameters for Targeted Drug Delivery journal July 2006
Particle size-dependent organ distribution of gold nanoparticles after intravenous administration journal April 2008
Biodistribution of colloidal gold nanoparticles after intravenous administration: Effect of particle size journal October 2008
Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles journal April 2009
Protracted elimination of gold nanoparticles from mouse liver journal June 2009
Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery journal May 2009
Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation journal September 1992
Establishment and characterization of a new human hepatocellular carcinoma cell line journal June 1984

Cited By (2)

Development and Characterization of Two-Dimensional Gratings for Single-Shot X-ray Phase-Contrast Imaging journal March 2018
Development and Characterization of Two-Dimensional Gratings for Single-Shot X-ray Phase-Contrast Imaging text January 2018