Details

Project TitleGd(III)-Dithiolane Gold Nanoparticle Conjugates for MRI of the Pancreas
Track Code2015-108
Short Description

A lipoic acid functionalized Gd(III)-gold nanoparticle conjugate as  a MRI contrast.

#diagnostics  #nanoparticles #therapeutics #imaging #theranostics

Abstract

Pancreatic adenocarcinoma has a 5 year survival of approximately 3% and median survival of 6 months and is among the most dismal of prognoses in all of medicine. This poor prognosis is largely due to delayed diagnosis where patients remain asymptomatic until advanced disease is present. Therefore, techniques to allow early detection of pancreatic adenocarcinoma are desperately needed. Imaging of pancreatic tissue is notoriously difficult, and the development of new imaging techniques would impact our understanding of organ physiology and pathology with applications in disease diagnosis, staging, and longitudinal response to therapy in vivo. Magnetic resonance imaging (MRI) provides numerous advantages for these types of investigations; however, it is unable to delineate the pancreas due to low inherent contrast within this tissue type.  To overcome this limitation, Northwestern researchers have prepared a new Gd(III) contrast agent that accumulates in the pancreas and provides significant contrast enhancement by MR imaging. They have synthesized and characterized a new dithiolane-Gd(III) complex and developed a straightforward and scalable approach for conjugation to a gold nanoparticle.  The nanoconjugates exhibit very high per particle values of r1 relaxivity at both low and high magnetic field strengths due to the high Gd(III) payload.  They have preliminary evidence of pancreatic tissue labeling that includes MR images, post-mortem biodistribution analysis, and pancreatic tissue evaluation of particle localization. Significant contrast enhancement was observed allowing clear identification of the pancreas with contrast-to-noise ratios exceeding 35:1. This technology allows for in vivo tracking via MRI of disease progression, enabling 3D and real time resolution, both of which are not possible with current techniques. 

Visualization and localization of Gd(III)-Dithiolane gold nanoparticle in the pancreas.

 
TagsHEALTHCARE: MRI, HEALTHCARE: imaging, nanotechnology: nanoparticles, theranostics
 
Posted DateMar 6, 2017 10:31 AM

Inventors

Thomas J. Meade*

Matthew W. Rotz

Robert J. Holbrook

Applications

  • Clinical diagnostics: MRI contrast agents
  • Theranostics:  Incorporation of both diagnostic and therapeutic entities into a single formulation
  • Tissue specific contrast agent: Accumulate in pancreatic tissue and monitor pancreatic tumor progression
  • Technology to functionalize nanoparticles with MRI agents, for their in vivo studies.

Advantages

  • Capability to post-modify any gold nanoparticle with a Gd(III) contrasting agent for MRI application
  • Improved spatial and temporal resolution than PET, bioluminescence, CT, and ultrasound
  • Extremely high Gd(lll} chelate loading on the particles surface
  • Variability of synthesized forms
  • Straightforward conjugation procedure
  • Applicable to other shapes of gold nanoparticles, including gold nanostars.
  • Capability to form complexes with other relevant biological metals (e.g., radionuclides 99mTc (SPECT}, 64Cu, 68Ga (PET)) with fast metalation kinetics and high thermodynamic stability constants, in addition to fast particle binding

Publications

Holbrook RJ, Rammohan N, Rotz MW, MacRenaris KW, Preslar AT, Meade TJ (2016) Gd(III)-Dithiolane Gold Nanoparticles for T1-Weighted Magnetic Resonance Imaging of the Pancreas. Nano Letters. 16: 3202-3209.

IP Status

US (15/192,377) and International patent applications (PCT/US2016/039300) have been filed.

Contact Information

Zachary Brown, PhD

Invention Associate
(p) 847.491.4629

(e) zachary.brown@northwestern.edu

Files

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