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Updated: May 20, 2025
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Development and preclinical evaluation of a gallium-68 labeled novel diagnostic tracer for visualizing ALK expression
Zhen-Peng Yu1, Ke-Xin Sun1, Dan Zhang1
1Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China.
Abstract:
Anaplastic lymphoma kinase (ALK) is prominently expressed in numerous malignant tumors, which lead to aberrant tumor proliferation, invasion and metastasis. Ceritinib (LDK378), as second-generation targeted drugs, has been used to treat advanced ALK-positive non-small cell lung cancer (NSCLC). Herein, we sought to develop a novel ALK-positron emission tomography/magnetic resonance (PET/MR) tracer 68Ga-DOTA-CTB (68Ga labeled ceritinib) based on ceritinib scaffold to monitor the ALK expression levels during targeted therapy with ceritinib. The 68Ga-DOTA-CTB radiotracer, obtained via a simple labeling procedure, exhibits favorable radiochemical purity, stability, and pharmacokinetic properties. Subsequently, cellular uptake experiments have demonstrated that 68Ga-DOTA-CTB could be accumulated in H2228 cells. Imaging and biodistribution experiments have revealed significant uptake of the radiotracer in the tumors of the experimental group, while tumors in the blocking group, which were saturated with an excess of precursor, exhibited a markedly reduced level of radioactivity. These empirical findings suggest that 68Ga-DOTA-CTB holds substantial potential as a novel PET/MR imaging tracer for ALK-positive tumors.
Insights
A new imaging tracer, 68Ga-DOTA-CTB, was developed to visualize anaplastic lymphoma kinase (ALK) expression in tumors. This tracer shows promise for monitoring ALK-positive cancers during targeted therapy.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Anaplastic lymphoma kinase (ALK) is a key driver in various cancers, promoting tumor growth and spread.
- Ceritinib is a targeted therapy for advanced ALK-positive non-small cell lung cancer (NSCLC).
- Monitoring ALK expression is crucial for effective targeted therapy.
Purpose of the Study:
- To develop a novel positron emission tomography/magnetic resonance (PET/MR) imaging tracer, 68Ga-DOTA-CTB, based on the ceritinib scaffold.
- To evaluate the potential of 68Ga-DOTA-CTB for monitoring anaplastic lymphoma kinase (ALK) expression levels in vivo.
- To assess the tracer's utility in tracking response to ceritinib-based targeted therapy.
Main Methods:
- Synthesis and characterization of the 68Ga-DOTA-CTB radiotracer.
- In vitro cellular uptake studies using ALK-positive cell lines (H2228).
- In vivo imaging and biodistribution studies in tumor-bearing models, including blocking experiments.
Main Results:
- 68Ga-DOTA-CTB was successfully synthesized with high radiochemical purity and stability.
- The tracer demonstrated significant accumulation in ALK-positive H2228 cells.
- In vivo studies showed specific tumor uptake, which was significantly reduced in the presence of excess unlabeled ceritinib, confirming target engagement.
Conclusions:
- 68Ga-DOTA-CTB is a promising novel PET/MR imaging tracer for visualizing ALK expression.
- The tracer facilitates non-invasive monitoring of ALK status in tumors.
- 68Ga-DOTA-CTB holds potential for guiding and evaluating targeted therapies in ALK-driven malignancies.
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