Development and biological evaluation of a novel CEACAM6-targeted PET tracer for distinguishing malignant nodules in early-stage lung adenocarcinoma
- Keying Zhu 1, Shimin Tang 1, Donghui Pan 2, Xinyu Wang 2, Yuping Xu 2, Junjie Yan 2, Lizhen Wang 2, Chongyang Chen 3, Min Yang 4,5
- Keying Zhu 1, Shimin Tang 1, Donghui Pan 2
- 1School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
- 2NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 214063, Wuxi, China.
- 3NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 214063, Wuxi, China. chenchongyang@jsinm.org.
- 4School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. yangmin@jsinm.org.
- 5NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 214063, Wuxi, China. yangmin@jsinm.org.
- 0School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
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View abstract on PubMed
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.
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