Noninvasive localization of tumors by immunofluorescence imaging using a single chain Fv fragment of a human monoclonal antibody with broad cancer specificity.
BACKGROUND
A single chain antibody fragment, NovoMAb-G2-scFv, derived from a human anti-tumor monoclonal antibody recognizes tumor antigen molecules expressed on a wide variety of human cancers including melanoma, breast carcinoma, colon adenocarcinoma, squamous cell carcinoma, lung carcinoma, and prostate carcinoma. This study was designed to evaluate the use of a NovoMab-G2-scFv/cyanine fluorochrome (Cy5.5.18) conjugate as diagnostic tool for in vivo imaging of tumors.


METHODS
The NovoMab-G2-scFv-Cy5 complex was administered to athymic mice injected subcutaneously with human melanoma tumor cells, and the distribution of fluorescence was imaged noninvasively using a charge-coupled device camera. Images were acquired 2, 6, 12, 24, 48, and 72 hours after injection.


RESULTS
Fluorescence was detected at the tumor site after injection of NovoMab-G2-scFv-Cy5 but not after injection of a labeled irrelevant control antibody fragment. Fluorescence from the tumor site peaked 2 hours after injection and gradually declined, reaching a minimum 72 hours after injection. Fluorescence was also apparent in the kidneys, indicating clearance of the complex through the kidneys. Results suggest that 16% and 73% of the antibody is located in the tumor and kidneys, respectively. Imaging of isolated organs confirmed the presence of the NovoMab-G2-scFv-Cy5 complex in tumors, kidneys, and liver. No fluorescence was observed in other organs.


CONCLUSIONS
Specific binding of the antibody-dye complex to the tumor was observed, and the kinetics of binding to tumors and kidneys were determined. These results suggest that the NovoMab-G2-scFv-Cy5.5 complex may be used for noninvasive tumor localization.
Ramjiawan
B
B
Institute for Biodiagnostics, Winnipeg, Manitoba, Canada.
Maiti
P
P
Aftanas
A
A
Kaplan
H
H
Fast
D
D
Mantsch
H H
HH
Jackson
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000918:Antibody Specificity; D004195:Disease Models, Animal; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007128:Immunoglobulin Fragments; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007128:Immunoglobulin Fragments