Background and Aims: Accurate endoscopic detection of premalignant lesions and earlycancers in the colon is essential for cure, since prognosis is closely related to lesion size andstage. Although it has great clinica...Background and Aims: Accurate endoscopic detection of premalignant lesions and earlycancers in the colon is essential for cure, since prognosis is closely related to lesion size andstage. Although it has great clinical potential, autofluorescence endoscopy has limited tumorto-normal tissue image contrast for detecting small preneoplastic lesions. We have developed amolecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate whichtargets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescencebased endoscopy of colon cancer. Methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T)subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivowhole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours postinjection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstratedthat modification of CC49 antibodies did not alter their specific tumor-localizing properties, andwas antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probetargeting a tumor-associated mucin detects colonic tumors at the molecular level in real time,and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.展开更多
文摘Background and Aims: Accurate endoscopic detection of premalignant lesions and earlycancers in the colon is essential for cure, since prognosis is closely related to lesion size andstage. Although it has great clinical potential, autofluorescence endoscopy has limited tumorto-normal tissue image contrast for detecting small preneoplastic lesions. We have developed amolecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate whichtargets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescencebased endoscopy of colon cancer. Methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T)subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivowhole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours postinjection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstratedthat modification of CC49 antibodies did not alter their specific tumor-localizing properties, andwas antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probetargeting a tumor-associated mucin detects colonic tumors at the molecular level in real time,and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.
