Method of Preparing 

Macromolecular Contrast Agents 

and Uses Thereof

Martin Brechbiel, Ph.D. and Kido Nwe, Ph.D.

Radioimmune & Inorganic Chemistry Section

Radiation Oncology Branch

Center for Cancer Research

National Cancer Institute

National Institutes of Health

10/06/2009 Slide #1

U.S. Department of Health and Human Services

National Institutes of Health
10/06/2009 Slide #2

Technology

Problem  Macromolecular MR contrast agents are:

difficult to characterize;

results are complex mixtures;

unstable Gd(III) complexes;

less than expected molar relaxivity.

Stage of research  pre-clinical in vivo

Patent Status – Filed 2009

Recent Publication:

Nwe, K., et al., Bioconjugate Chem. 2009, 20, 1412-1418. 

Related Patent:

Gansow, O. A., Brechbiel, M. B., Magerstadt, M. A.: Complexes of Functionalized 

Tetraazacyclododecane Chelates with Bismuth, Lead, Yttrium, Actinium, or 

Lanthanide Metal Ions. U.S. Patent 5,428,154

U.S. Department of Health and Human Services

National Institutes of Health
Technology Applications

Areas in which the technology can be applied

All macromolecular Gd(III) MR contrast agents

All macromolecular Gd(III) MR contrast agents that are combined 

with other imaging modalities.

Impacts LMW Gd(III) MR contrast agents 

Why is it important? Why is it different?

Simplifies characterization concerns  Reproducible chemistry

Eliminates toxicity concerns  kinetically inert complex

Enhances molar relaxivity  decreases required injected dose

Validation

In vivo animal imaging

Proper formation of Gd(III) complexes 

10/06/2009 Slide #3

U.S. Department of Health and Human Services

National Institutes of Health
Commercial Applications

MRI contrast agents with greatly improved 

homogeneity and stability

Greater molar relaxivity, allows using much less of the 

agent than previously required to acquire comparable 

or better images

10/06/2009 Slide #4

U.S. Department of Health and Human Services

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Dendrimer–based gadolinium chelates exhibit 

large proton relaxation enhancements

Weiner, Brechbiel, Brothers, Magin, Gansow, Tomalia, Lauterbur, Mag. Res. Med. 1994, 31, 1-8.

U.S. Department of Health and Human Services

National Institutes of Health
Dendrimer –based using pre-formed CDOTA chelated Gd+3 exhibit Larger proton 

relaxation enhancements!

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Frequency (MHz)

R1 (mMsec)-1

Magnevist Prohance G4 (DOTA[Gd]) G5 (DOTA[Gd]) G6 (DOTA[Gd])

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Frequency (MHz)

R2 (mMsec)-1
G4-(1B4M-DTPA-Gd)30

In vivo imaging – pre-Gd+3 incorporation 

DTPA vs. C-DOTA 

G4-(C-DOTA-Gd)28

U.S. Department of Health and Human Services

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Collaboration Opportunities

Licensing and/or CRADA opportunities

Future research  actively targeted agents

What would you want out of a collaboration?

• Novel targets & targeting vectors w/ corresponding animal 

models

• Access to imaging instrumentation

Available for licensing?  YES!

10/06/2009 Slide #8

U.S. Department of Health and Human Services

National Institutes of Health
Contact Information

For further information contact:

Licensing:

Eric W. Odom, Ph.D.

NIH Office of Technology Transfer (OTT)

Tel.: 301-435-5009

odome@mail.nih.gov

Collaboration:

Thomas P. Clouse, Ph.D. 

NCI Technology Transfer Center

301.594.1903

clouset@mail.nih.gov

10/06/2009 Slide #9

U.S. Department of Health and Human Services

National Institutes of Health