A nanobody targeting carcinoembryonic antigen as a promising molecular probe for non-small cell lung cancer

Mol Med Rep. 2017 Jul;16(1):625-630. doi: 10.3892/mmr.2017.6677. Epub 2017 Jun 1.

Abstract

Carcinoembryonic antigen (CEA) is a biomarker and therapy target for non‑small cell lung cancer (NSCLC), which is the most common type of lung cancer. Nanobodies with high target specificity are promising candidates to function as anti‑CEA probes. In the present study, the targeting effects of an anti‑CEA nanobody obtained from phage display were investigated using technetium‑99 m (99mTc) and fluorescence labeling. In vitro binding and immunofluorescent staining assays, as well as in vivo blood clearance and biodistribution assays were performed. High specificity and affinity of the nanobody for CEA‑positive H460 cells was observed in vitro. The pharmacokinetics assay of the 99mTc‑nanobody in Wistar rats demonstrated that the nanobody had appropriate T1/2α and T1/2β, which were 20.2 and 143.5 min, respectively. The biodistribution assay using H460 xenograft‑bearing nude mice demonstrated a high ratio of signal in tumor compared with background, which confirmed that the nanobody may be useful as a molecular probe for CEA‑positive cancer, particularly in NSCLC.

MeSH terms

  • Animals
  • Carcinoembryonic Antigen / blood*
  • Carcinoembryonic Antigen / immunology
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Fluorescent Antibody Technique*
  • Heterografts
  • Humans
  • Isotope Labeling
  • Lung Neoplasms / blood*
  • Lung Neoplasms / diagnosis*
  • Molecular Probes
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / isolation & purification
  • Radiopharmaceuticals / pharmacokinetics
  • Single-Domain Antibodies* / administration & dosage
  • Single-Domain Antibodies* / immunology
  • Single-Domain Antibodies* / isolation & purification
  • Technetium
  • Tissue Distribution

Substances

  • Carcinoembryonic Antigen
  • Molecular Probes
  • Radiopharmaceuticals
  • Single-Domain Antibodies
  • Technetium-99
  • Technetium