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

Chem Biol Drug Des. 2015 Jun;85(6):696-701. doi: 10.1111/cbdd.12459. Epub 2014 Nov 15.

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.

Keywords: SPECT; Tc-99m; anti-CD11b antibody; colon cancer; inflammation; myeloid-derived suppressor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • CD11b Antigen
  • Immunoconjugates
  • Organotechnetium Compounds