Development and biological evaluation of a novel CEACAM6-targeted PET tracer for distinguishing malignant nodules in early-stage lung adenocarcinoma

  • 0School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.

Summary

This summary is machine-generated.

A novel PET imaging tracer, [68Ga]Ga-NODA-P3, shows promise for visualizing CEACAM6-positive lung adenocarcinoma (LUAD). Further optimization is needed for clinical use in diagnosing malignant pulmonary nodules.

Area Of Science

  • Oncology
  • Radiochemistry
  • Molecular Imaging

Background

  • Low-dose CT (LDCT) screening reduces lung adenocarcinoma (LUAD) mortality but distinguishing malignant nodules is challenging.
  • Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) is a potential biomarker for LUAD, offering a target for noninvasive diagnosis.
  • Positron emission tomography (PET) imaging can leverage biomarkers for enhanced diagnostic capabilities.

Purpose Of The Study

  • To investigate the expression specificity of CEACAM6 in LUAD.
  • To develop and evaluate a novel PET imaging tracer targeting CEACAM6 for LUAD diagnosis.
  • To assess the potential of CEACAM6-targeted PET imaging in differentiating malignant pulmonary nodules.

Main Methods

  • Analysis of LUAD patient datasets (mRNA, protein, survival) and a murine model to study CEACAM6 expression.
  • Design and synthesis of CEACAM6-targeting ligands using the Rosetta platform.
  • [68Ga]Ga labeling and high-throughput PET imaging screening to identify optimal radiotracers.

Main Results

  • CEACAM6 is specifically overexpressed in LUAD, correlating with poor prognosis and disease progression.
  • [68Ga]Ga-NODA-P3 demonstrated high specificity for CEACAM6-positive LUAD xenografts in PET imaging.
  • The tracer achieved a high target-to-background ratio and significantly higher uptake in LUAD models compared to controls.

Conclusions

  • Preclinical data suggest [68Ga]Ga-NODA-P3 is a viable candidate radiotracer for visualizing CEACAM6-positive LUAD.
  • The tracer exhibits favorable imaging contrast, supporting its potential for noninvasive diagnosis.
  • Ongoing optimization is necessary to enhance tumor uptake for immediate clinical application in diagnosing malignant pulmonary nodules.