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 car cinoma, colon adenocarcinoma, squamous cell carcinoma, lung carcinoma, and prostate carcinoma. This study was designed to evaluate the use of a NovoMa b-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 i njected subcutaneously with human melanoma tumor cells, and the distributio n of fluorescence was imaged noninvasively using a charge-coupled device ca mera. Images were acquired 2, 6, 12, 24, 48, and 72 hours after injection. RESULTS, Fluorescence was detected at the tumor site after injection of Nov oMab-G2-scFv-Cy5 but not after injection of a labeled irrelevant control an tibody fragment. Fluorescence from the tumor site peaked 2 hours after inje ction 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 antibo dy is located in the tumor and kidneys, respectively. Imaging of isolated o rgans 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. (C) 2000 American Cancer Society.