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Preparation and Evaluation of 99mTc‐labeled anti‐CD11b Antibody Targeting Inflammatory Microenvironment for Colon Cancer Imaging
Authors:Dengfeng Cheng  Weihong Zou  Xiao Li  Yan Xiu  Hui Tan  Hongcheng Shi  Xiangdong Yang
Affiliation:1. Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China;2. Shanghai Institute of Medical Imaging, Shanghai, China;3. Department of Pharmacy, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China;4. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, FudanUniversity, Shanghai, China
Abstract:CD11b, an active constituent of innate immune response highly expressed in myeloid‐derived suppressor cells (MDSCs), can be used as a marker of inflammatory microenvironment, particularly in tumor tissues. In this research, we aimed to fabricate a 99mTc‐labeled anti‐CD11b antibody as a probe for CD11b+ myeloid cells in colon cancer imaging with single‐photon emission computed tomography (SPECT). In situ murine colon tumor model was established in histidine decarboxylase knockout (Hdc?/?) mice by chemicals induction. 99mTc‐labeled anti‐CD11b was obtained with labeling yields of over 30% and radiochemical purity of over 95%. Micro‐SPECT/CT scans were performed at 6 h post injection to investigate biodistributions and targeting of the probe. In situ colonic neoplasma as small as 3 mm diameters was clearly identified by imaging; after dissection of the animal, anti‐CD11b immunofluorescence staining was performed to identify infiltration of CD11b+ MDSCs in microenvironment of colonic neoplasms. In addition, the images displayed intense signal from bone marrow and spleen, which indicated the origin and migration of CD11b+ MDSCs in vivo, and these results were further proved by flow cytometry analysis. Therefore, 99mTc‐labeled anti‐CD11b SPECT displayed the potential to facilitate the diagnosis of colon tumor in very early stage via detection of inflammatory microenvironment.
Keywords:anti‐CD11b antibody  colon cancer  inflammation  myeloid‐derived suppressor cells     SPECT     Tc‐99m
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