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Tri-functional Imaging Agent for Monoclonal Antibody Tumor-Targeted Imaging

Posted Aug 04 2013 8:00pm

Description of Invention:
This is a novel lysine-based trifunctional chelate which bears both a chelating moiety (CHX-A") for sequestering radiometals (86Y or 111In) and a near-infrared dye, e.g., Cy5.5, for dual modality PET (or SPECT) and fluorescence imaging. Successful conjugation of monoclonal antibody trastuzumab (Herceptin) or cetuximab (Erbitux), has also been achieved by efficient thiol-maleimide chemistry, thereby yielding an immunoconjugate (Signaling agent (Cy5.5-Lys(SMCC)-CHX-A") conjugated to trastuzumab) or (Signaling agent (Cy7-Lys(SMCC)-CHX-A") conjugated to cetuximab). Both specifically target antigen expressing cells and internalization of the agent has been imaged over time. Trastuzumab can be radiolabeled with isothiocyanate derivatives of the bifunctional chelating agents 1B4M (2-(4-aminobenzy1)-6-methyldiethylenetriaminepentaacetic acid); and CHX-A" (N-[(R)-2-amino-3-(p-aminophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N",N"-pentaacetic acid).

Applications:
  • Cancer imaging
  • Cancer diagnostics


Advantages:
  • Target specific
  • Multifunctional (imageable through multiple platforms)


Development Status:
  • Early-stage
  • In vivo data available (animal)


Inventors:
Martin W Brechbiel (NCI)
Heng Xu (NCI)
Kwamena E Baidoo (NCI)


Patent Status:
HHS, Reference No. E-194-2007/0
US, Application No. 12/667,790 filed 05 Jan 2010


Related Technologies:
US, Application No. 61/779,016 filed 13 Mar 2013, Reference No. E-111-2013/0


Relevant Publication:
  1. Xu H, et al. [ PMID 17725340 ]
  2. Nayak TK, et al. [ PMID 22213822 ]
  3. Dadwal M, et al. [ PMID 22047687 ]
  4. Song HA, et al. [ PMID 21604692 ]
  5. Bumb A, et al. [ PMID 20368682 ]


Collaborative Research Opportunity:
The National Cancer Institute Radiation Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, Trifunctional Imaging Agent for Monoclonal Antibody Tumor-Targeted Imaging. For collaboration opportunities, please contact John D. Hewes, Ph.D. at hewesj@mail.nih.gov for more information.


For Licensing Information Please Contact:
Michael Shmilovich Esq.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: shmilovm@mail.nih.gov
Phone: 301-435-5019
Fax: 301-402-0220


Ref No: 1691

Updated: 08/2013

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