skip to main content
DOE PAGES 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

Abstract

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.

Authors:
 [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)
Publication Date:
Research Org.:
Brown Univ., Providence, RI (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1239142
Grant/Contract Number:  
FG02-08ER15937
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; cancer imaging; imaging techniques and agents; translational research

Citation Formats

Rand, Danielle, Derdak, Zoltan, Carlson, Rolf, Wands, Jack R., and Rose-Petruck, Christoph. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents. United States: N. p., 2015. Web. doi:10.1038/srep15673.
Rand, Danielle, Derdak, Zoltan, Carlson, Rolf, Wands, Jack R., & Rose-Petruck, Christoph. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents. United States. doi:10.1038/srep15673.
Rand, Danielle, Derdak, Zoltan, Carlson, Rolf, Wands, Jack R., and Rose-Petruck, Christoph. Thu . "X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents". United States. doi:10.1038/srep15673. https://www.osti.gov/servlets/purl/1239142.
@article{osti_1239142,
title = {X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents},
author = {Rand, Danielle and Derdak, Zoltan and Carlson, Rolf and Wands, Jack R. and Rose-Petruck, Christoph},
abstractNote = {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.},
doi = {10.1038/srep15673},
journal = {Scientific Reports},
number = ,
volume = 5,
place = {United States},
year = {2015},
month = {10}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 1 work
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Functional imaging techniques in hepatocellular carcinoma
journal, March 2012

  • Goh, V.; Sarker, D.; Osmany, S.
  • European Journal of Nuclear Medicine and Molecular Imaging, Vol. 39, Issue 6
  • DOI: 10.1007/s00259-012-2096-x

Global cancer statistics
journal, February 2011

  • Jemal, Ahmedin; Bray, Freddie; Center, Melissa M.
  • CA: A Cancer Journal for Clinicians, Vol. 61, Issue 2
  • DOI: 10.3322/caac.20107

Recent advances in the natural history of hepatocellular carcinoma
journal, May 2008

  • Trevisani, F.; Cantarini, M. C.; Wands, J. R.
  • Carcinogenesis, Vol. 29, Issue 7
  • DOI: 10.1093/carcin/bgn113

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

  • Murakami, Takamichi; Imai, Yasuharu; Okada, Masahiro
  • Oncology, Vol. 81, Issue s1
  • DOI: 10.1159/000333267

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

  • Wen, H.; Bennett, E. E.; Hegedus, M. M.
  • IEEE Transactions on Medical Imaging, Vol. 27, Issue 8
  • DOI: 10.1109/TMI.2007.912393

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

  • Stein, Ashley F.; Ilavsky, Jan; Kopace, Rael
  • Optics Express, Vol. 18, Issue 12
  • DOI: 10.1364/OE.18.013271

Nanomaterials for X-ray Imaging: Gold Nanoparticle Enhancement of X-ray Scatter Imaging of Hepatocellular Carcinoma
journal, July 2011

  • Rand, Danielle; Ortiz, Vivian; Liu, Yanan
  • Nano Letters, Vol. 11, Issue 7
  • DOI: 10.1021/nl200858y

X-ray spatial harmonic imaging of phase objects
journal, January 2011

  • Liu, Yanan; Ahr, Brian; Linkin, Alexander
  • Optics Letters, Vol. 36, Issue 12
  • DOI: 10.1364/OL.36.002209

X-ray spatial frequency heterodyne imaging
journal, February 2012

  • Wu, Binbin; Liu, Yanan; Rose-Petruck, Christoph
  • Applied Physics Letters, Vol. 100, Issue 6
  • DOI: 10.1063/1.3681794

Hard-X-ray dark-field imaging using a grating interferometer
journal, January 2008

  • Pfeiffer, F.; Bech, M.; Bunk, O.
  • Nature Materials, Vol. 7, Issue 2, p. 134-137
  • DOI: 10.1038/nmat2096

The First Analysis and Clinical Evaluation of Native Breast Tissue Using Differential Phase-Contrast Mammography
journal, January 2011


Hard X-ray dark-field imaging with incoherent sample illumination
journal, January 2014

  • Endrizzi, Marco; Diemoz, Paul C.; Millard, Thomas P.
  • Applied Physics Letters, Vol. 104, Issue 2
  • DOI: 10.1063/1.4861855

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

  • Hainfeld, J. F.; Slatkin, D. N.; Focella, T. M.
  • The British Journal of Radiology, Vol. 79, Issue 939
  • DOI: 10.1259/bjr/13169882

Antibiofouling Polymer-Coated Gold Nanoparticles as a Contrast Agent for in Vivo X-ray Computed Tomography Imaging
journal, June 2007

  • Kim, Dongkyu; Park, Sangjin; Lee, Jae Hyuk
  • Journal of the American Chemical Society, Vol. 129, Issue 24
  • DOI: 10.1021/ja071471p

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

  • Popovtzer, Rachela; Agrawal, Ashish; Kotov, Nicholas A.
  • Nano Letters, Vol. 8, Issue 12
  • DOI: 10.1021/nl8029114

A highly sensitive x-ray imaging modality for hepatocellular carcinoma detection in vitro
journal, January 2015

  • Rand, Danielle; Walsh, Edward G.; Derdak, Zoltan
  • Physics in Medicine and Biology, Vol. 60, Issue 2
  • DOI: 10.1088/0031-9155/60/2/769

X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents
journal, January 2014

  • Rand, Danielle; Uchida, Masaki; Douglas, Trevor
  • Optics Express, Vol. 22, Issue 19
  • DOI: 10.1364/OE.22.023290

Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles
journal, May 2008

  • Alexis, Frank; Pridgen, Eric; Molnar, Linda K.
  • Molecular Pharmaceutics, Vol. 5, Issue 4
  • DOI: 10.1021/mp800051m

In Pursuit of Zero: Polymer Brushes that Resist the Adsorption of Proteins
journal, June 2009

  • Hucknall, Angus; Rangarajan, Srinath; Chilkoti, Ashutosh
  • Advanced Materials, Vol. 21, Issue 23, p. 2441-2446
  • DOI: 10.1002/adma.200900383

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

  • Brandenberger, Christina; Mühlfeld, Christian; Ali, Zulqurnain
  • Small, Vol. 6, Issue 15
  • DOI: 10.1002/smll.201000528

Zero-length crosslinking procedure with the use of active esters
journal, February 1990


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

  • Gole, Anand; Murphy, Catherine J.
  • Langmuir, Vol. 21, Issue 23
  • DOI: 10.1021/la0512704

Engineering of Hetero-Functional Gold Nanorods for the in vivo Molecular Targeting of Breast Cancer Cells
journal, January 2009

  • Eghtedari, Mohammad; Liopo, Anton V.; Copland, John A.
  • Nano Letters, Vol. 9, Issue 1
  • DOI: 10.1021/nl802915q

Cyclodextrin-covered gold nanoparticles for targeted delivery of an anti-cancer drug
journal, January 2009

  • Park, Chiyoung; Youn, Hyewon; Kim, Hana
  • Journal of Materials Chemistry, Vol. 19, Issue 16
  • DOI: 10.1039/b816209c

Design and Characterization of HER-2-Targeted Gold Nanoparticles for Enhanced X-radiation Treatment of Locally Advanced Breast Cancer
journal, September 2010

  • Chattopadhyay, Niladri; Cai, Zhongli; Pignol, Jean-Philippe
  • Molecular Pharmaceutics, Vol. 7, Issue 6
  • DOI: 10.1021/mp100207t

Rapid Uptake of Gold Nanorods by Primary Human Blood Phagocytes and Immunomodulatory Effects of Surface Chemistry
journal, May 2010

  • Bartneck, Matthias; Keul, Heidrun A.; Singh, Smriti
  • ACS Nano, Vol. 4, Issue 6
  • DOI: 10.1021/nn100262h

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

  • Roberts, R. A.; Ganey, P. E.; Ju, C.
  • Toxicological Sciences, Vol. 96, Issue 1
  • DOI: 10.1093/toxsci/kfl173

Kupffer cells are central in the removal of nanoparticles from the organism
journal, January 2007

  • Sadauskas, Evaldas; Wallin, Håkan; Stoltenberg, Meredin
  • Particle and Fibre Toxicology, Vol. 4, Issue 1
  • DOI: 10.1186/1743-8977-4-10

A conjugate of 5-fluorouridine-poly(L-lysine) and an antibody reactive with human colon carcinoma
journal, July 1990

  • Hurwitz, E.; Stancovski, I.; Wilchek, M.
  • Bioconjugate Chemistry, Vol. 1, Issue 4
  • DOI: 10.1021/bc00004a010

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

  • Paciotti, Giulio F.; Myer, Lonnie; Weinreich, David
  • Drug Delivery, Vol. 11, Issue 3, p. 169-183
  • DOI: 10.1080/10717540490433895

Gold Nanoparticles as a Versatile Platform for Optimizing Physicochemical Parameters for Targeted Drug Delivery
journal, July 2006

  • Bergen, Jamie M.; von Recum, Horst A.; Goodman, Thomas T.
  • Macromolecular Bioscience, Vol. 6, Issue 7
  • DOI: 10.1002/mabi.200600075

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

  • Sonavane, Ganeshchandra; Tomoda, Keishiro; Makino, Kimiko
  • Colloids and Surfaces B: Biointerfaces, Vol. 66, Issue 2
  • DOI: 10.1016/j.colsurfb.2008.07.004

Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles
journal, April 2009

  • Cho, Wan-Seob; Cho, Minjung; Jeong, Jinyoung
  • Toxicology and Applied Pharmacology, Vol. 236, Issue 1
  • DOI: 10.1016/j.taap.2008.12.023

Protracted elimination of gold nanoparticles from mouse liver
journal, June 2009

  • Sadauskas, Evaldas; Danscher, Gorm; Stoltenberg, Meredin
  • Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 5, Issue 2
  • DOI: 10.1016/j.nano.2008.11.002

Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery
journal, May 2009

  • Terentyuk, Georgy S.; Maslyakova, Galina N.; Suleymanova, Leyla V.
  • Journal of Biophotonics, Vol. 2, Issue 5
  • DOI: 10.1002/jbio.200910005

Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation
journal, September 1992

  • Hardonk, M. J.; Dijkhuis, F. W. J.; Hulstaert, C. E.
  • Journal of Leukocyte Biology, Vol. 52, Issue 3
  • DOI: 10.1002/jlb.52.3.296

Establishment and characterization of a new human hepatocellular carcinoma cell line
journal, June 1984

  • He, Lun; Isselbacher, Kurt J.; Wands, Jack R.
  • In Vitro, Vol. 20, Issue 6
  • DOI: 10.1007/BF02619623