Superparamagnetic Nanocomplexes and Their Use as Contrast Agents in MRI

Description of Invention:
The invention offered for licensing and commercial development relates to the fields of cell therapy and tracking of such therapy by magnetic resonance imaging. More specifically the technology describes novel superparamagnetic magnetic resonance contrast agents, methods of making the agents, and methods of labeling cells with the contrast agents and imaging the labeled cells using magnetic resonance.

The self assembled agents are composed of three (3) components: Superparamagnetic iron oxide nanoparticle (e.g. F₃O₄), associated with a carbohydrate coating (e.g., a polycation (e.g., Protamine Sulfate); and a polycation (e.g., glycosaminoglycan:Heparin). Self-assembling superparamagnetic nanocomplexes made from simple commercially available chemicals such as Heparin sulfate (H), Protamine sulfate (P), and Ferumoxytol nanocomplexes (HPF nanocomplexes) can effectively label stem cells, immune cells, tumor cells, or any other therapeutically engineered cells for cellular MRI. Biological cells can be labeled with the nanocomplexes by contacting cells under conditions sufficient to produce the nanocomplexes, or by contacting the cells with pre-assembled nanocomplexes. The labeled biological cells can be transplanted into an individual, imaged by MRI and the migration pattern and/or cellular distribution pattern of the labeled biological cells in the subject can then be detected. This technique will readily facilitate the tracking of the therapeutic cells, and thus render cell-based therapy and/or tissue repair more precise, accurate and effective.

Applications:
Clinical —

• Cell-based therapy (e.g. stem cells, or immune cells therapy, genetic engineered cells); monitoring and detecting cell trafficking and distribution
• Diagnostics

Research —

• Cell-based therapy
• Tissue regeneration

Advantages:

• Avoid radioactive labeling
• More efficient cell incorporation than the use of noncomplexed paramagnetic or superparamagnetic particles
• Non toxic
• Easily prepared from three (3) commercially available FDA approved drugs off label. No synthesis is required (self assembled)
• No FDA approved MRI contrast agent containing paramagnetic or superparamagnetic iron oxide nanoparticles

Development Status:

• The labeling complex has been repeatedly prepared. May require some further optimization for specific cell products and scale up.
• Incorporation into mammal cells has been demonstrated.

Inventors:
Joseph A Frank (CC)


Patent Status:
HHS, Reference No. E-285-2010/0
US, Application No. 61/439,106 filed 03 Feb 2011


Relevant Publication:

1. Frank JA, Anderson SA, Kalsih H, Lewis BK, Yocum GT, Arbab AS. Methods for magnetically labeling stem and other cells for detection by in vivo magnetic resonance imaging. Cytotherapy. 2004; 6(6):621-625. [ PubMed: 15773025 ]
2. Arbab AS, Liu W, Frank JA. Cellular magnetic resonance imaging: current status and future prospects. Expert Rev Med Devices. 2006 Jul;3(4):427-439. [ PubMed: 16866640 ]

Licensing Status:
Available for licensing and commercial development.

Collaborative Research Opportunity:
The Clinical Center, Frank Laboratory, Radiology and Imaging Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Joseph A. Frank MS MD at 301-402-4314 or jafrank@helix.nih.gov for more information.


Portfolios:
Devices/Instrumentation
Devices/Instrumentation - Research Tools and Materials
Internal Medicine
Internal Medicine - Therapeutics



For Licensing Information Please Contact:
John Stansberry Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: js852e@nih.gov
Phone: 301-435-5236
Fax: 301-402-0220


Ref No: 2244

Updated: 03/2011