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Article

Design, Synthesis, and Characterization of a Dual Modality Positron Emission Tomography and Fluorescence Imaging Agent for Monoclonal Antibody Tumor-Targeted Imaging

Supporting Info

Heng Xu,^§ Kwamena Baidoo,^§ Andrew J. Gunn,^† C. Andrew Boswell,^§ Diane E. Milenic,^§ Peter L. Choyke,^† and Martin W. Brechbiel*^§

Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1088, and Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1088

J. Med. Chem., 2007, 50 (19), pp 4759–4765

DOI: 10.1021/jm070657w

Publication Date (Web): August 29, 2007

Radiation Oncology Branch, National Cancer Institute.

†

Molecular Imaging Program, Center for Cancer Research, National Cancer Institute.

To whom correspondence should be addressed. Martin W. Brechbiel, Ph.D., Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, NCI, NIH, Building 10, Room 1B40, 10 Center Drive, Bethesda, Maryland 20892-1088. Phone: (301) 496-0591. Fax: (301) 402-1923. E-mail: martinwb@mail.nih.gov.

Abstract

A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A‘ ‘) for sequestering radiometals (⁸⁶Y or ¹¹¹In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the monoclonal antibody trastuzumab (Herceptin) was achieved by efficient thiol-maleimide chemistry, thereby yielding immunoconjugate 2. Analysis of 2 by flow cytometry and competitive binding assay demonstrates that immunoconjugate 2 binds to SKOV3 tumor cells comparably to native trastuzumab and, thus, may be used as a tumor-targeted monoclonal antibody probe for multimodality imaging.

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PDB: 1B4M

History

Published In Issue September 20, 2007
Received June 7, 2007

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Article

Design, Synthesis, and Characterization of a Dual Modality Positron Emission Tomography and Fluorescence Imaging Agent for Monoclonal Antibody Tumor-Targeted Imaging

Abstract

Tools

SciFinder Links

Accession Codes

History

Recommend & Share

Related Content

Toward Improved Syntheses of Dendrimer-Based Magnetic Resonance Imaging Contrast Agents: New Bifunctional Diethylenetriaminepentaacetic Acid Ligands and Nonaqueous Conjugation Chemistry

The Synthesis and Chelation Chemistry of DOTA−Peptide Conjugates

Validation of a Novel CHX-A‘ ‘ Derivative Suitable for Peptide Conjugation: Small Animal PET/CT Imaging Using Yttrium-86-CHX-A‘ ‘-Octreotide

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