Design, synthesis, and characterization of a dual modality positron emission tomography and fluorescence imaging agent for monoclonal antibody tumor-targeted imaging.
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.
Xu
Heng
H
Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1088, USA.
Baidoo
Kwamena
K
Gunn
Andrew J
AJ
Boswell
C Andrew
CA
Milenic
Diane E
DE
Choyke
Peter L
PL
Brechbiel
Martin W
MW
D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized; D001667:Binding, Competitive; D002232:Carbocyanines / Q000737:chemistry*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000378:metabolism; D007205:Indium Radioisotopes; D017879:Isothiocyanates / Q000737:chemistry*; D008239:Lysine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D049268:Positron-Emission Tomography; D011863:Radioimmunoassay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000068878:Trastuzumab; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D002614:Chelating Agents; D005456:Fluorescent Dyes; D018796:Immunoconjugates; D007205:Indium Radioisotopes; D017879:Isothiocyanates; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C085678:N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid; D004369:Pentetic Acid; D008239:Lysine; D000068878:Trastuzumab