Preparation and Evaluation of 99mTc-labeled anti-CD11b Antibody Targeting Inflammatory Microenvironment for Colon Cancer Imaging.

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 (99m)Tc-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. (99m)Tc-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, (99m)Tc-labeled anti-CD11b SPECT displayed the potential to facilitate the diagnosis of colon tumor in very early stage via detection of inflammatory microenvironment.

• Authors: Dengfeng Cheng, Weihong Zou, Xiao Li, Yan Xiu, Hui Tan, Hongcheng Shi, Xiangdong Yang
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 85 Issue 6 Pg. 696-701 (Jun 2015) ISSN: 1747-0285 [Electronic] England
• PMID: 25346241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S.

Chemical References

• CD11b Antigen
• Immunoconjugates
• Organotechnetium Compounds

Topics

• Animals
• CD11b Antigen (immunology)
• Colon (diagnostic imaging, immunology, pathology)
• Colonic Neoplasms (complications, diagnosis, diagnostic imaging, immunology)
• Immunoconjugates (chemistry, immunology)
• Inflammation (complications, diagnosis, diagnostic imaging, immunology)
• Mice, Inbred BALB C
• Organotechnetium Compounds (chemistry, immunology)
• Tomography, Emission-Computed, Single-Photon (methods)