Toward preparation of antibody-based imaging probe libraries for dual-modality positron emission tomography and fluorescence imaging.
Two novel imaging agents trastuzumab-Cy5.5-CHX-A''1 and cetuximab-Cy7-CHX-A''2, bearing both a chelating moiety (CHX-A'') for sequestering metallic radionuclides ((86)Y or (111)In) and the near infrared dye Cy5.5/Cy7, were prepared by a novel modular synthetic strategy as examples of dual-labeled, antibody-based imaging probe library. Fluorescent microscopy illustrated that 1 and 2 strongly bind to HER2-expressing cancer cells (e.g., NIH3T3-HER2(+), SKOV-3) and to EGFR-expressing cancer cells (e.g., A431), respectively, thereby demonstrating that the functionality of the targeting moiety is conserved. Hence, the described novel synthesis strategy can be applied to engineer other tumor-targeted monoclonal antibody based probes for multimodality imaging.
Xu
Heng
H
Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 1B40, 10 Center Drive, Bethesda, MD 20892-1088, USA.
Eck
Peter K
PK
Baidoo
Kwamena E
KE
Choyke
Peter L
PL
Brechbiel
Martin W
MW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D002232:Carbocyanines / Q000032:analysis / Q000737:chemistry; D045744:Cell Line, Tumor; D000068818:Cetuximab; D002614:Chelating Agents / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D049268:Positron-Emission Tomography; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism; D000068878:Trastuzumab; D015021:Yttrium Radioisotopes / Q000737:chemistry
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002232:Carbocyanines; D000068818:Cetuximab; D002614:Chelating Agents; D066246:ErbB Receptors; D005456:Fluorescent Dyes; D007205:Indium Radioisotopes; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D015021:Yttrium Radioisotopes; C098793:CY5.5 cyanine dye