In vivo molecular imaging to diagnose and subtype tumors through receptor-targeted optically labeled monoclonal antibodies.
Molecular imaging of cell surface receptors can potentially diagnose tumors based on their distinct expression profiles. Using multifilter spectrally resolved optical imaging with three fluorescently labeled antibodies, we simultaneously imaged three different cell surface receptors to distinguish tumor types noninvasively. We selected tumors overexpressing different subtypes of EGFR receptor: HER-1 (A431) and HER-2 (NIH3T3/HER2(+)), or interleukin-2 receptor alpha-subunit receptor (IL-2Ralpha; SP2/Tac). After tumor establishment, a cocktail of three fluorescently labeled monoclonal antibodies was injected: cetuximab-Cy5 (targetingHER-1), trastuzumab-Cy7(HER-2),anddaclizumab-AlexaFluor-700 (IL-2Ra). Optical fluorescence imaging was performed after 24 hours with both a red filter set and three successive filter sets (yellow, red, and deep red). Spectrally resolved imaging of 10 mice clearly distinguished A431, NIH3T3/HER2(+), and SP2-Tac tumors based on their distinct optical spectra. Three-filter sets significantly increased the signal-to-background ratio compared to a single-filter set by reducing the background signal, thus significantly improving the differentiation of each of the receptors targeted (P < .022). In conclusion, following multifilter spectrally resolved imaging, different tumor types can be simultaneously distinguished and diagnosed in vivo. Multiple filter sets increase the signal-to-noise ratio by substantially reducing the background signal, and may allow more optical dyes to be resolved within the narrow limits of the near-infrared spectrum.
Koyama
Yoshinori
Y
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 1B40, Bethesda, MD, 20892-1088, USA.
Barrett
Tristan
T
Hama
Yukihiro
Y
Ravizzini
Gregory
G
Choyke
Peter L
PL
Kobayashi
Hisataka
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D002232:Carbocyanines / Q000008:administration & dosage / Q000032:analysis; D000068818:Cetuximab; D000077561:Daclizumab; D066246:ErbB Receptors / Q000032:analysis* / Q000276:immunology; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis*; D006801:Humans; D018796:Immunoconjugates / Q000032:analysis*; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000032:analysis*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000145:classification / Q000175:diagnosis* / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000276:immunology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002232:Carbocyanines; D000068818:Cetuximab; D000077561:Daclizumab; D066246:ErbB Receptors; D005456:Fluorescent Dyes; D018796:Immunoconjugates; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508017:IL2RA protein, human; C085321:cyanine dye 5; C501744:indotricarbocyanine; C512478:EGFR protein, human; C524056:Erbb2 protein, mouse