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Updated: Jun 9, 2026
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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Development of a new epidermal growth factor receptor positron emission tomography imaging agent based on the
Federica Pisaneschi1, Quang-De Nguyen, Elham Shamsaei
1Comprehensive Cancer Imaging Centre, Department of Chemistry, Imperial College London, Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom. f.pisaneschi@imperial.ac.uk
Abstract:
The epidermal growth factor receptor (EGFR/c-ErbB1/HER1) is overexpressed in many cancers including breast, ovarian, endometrial, and non-small cell lung cancer. An EGFR specific imaging agent could facilitate clinical evaluation of primary tumors and/or metastases. To achieve this goal we designed and synthesized a small array of fluorine containing compounds based on a 3-cyanoquinoline core. A lead compound, 16, incorporating 2'-fluoroethyl-1,2,3-triazole was selected for evaluation as a radioligand based on its high affinity for EGFR kinase (IC50=1.81+/-0.18 nM), good cellular potency (IC50=21.97+/-9.06 nM), low lipophilicity and good metabolic stability. 'Click' labeling afforded [18F]16 in 37.0+/-3.6% decay corrected radiochemical yield based on azide [18F]14 and 7% end of synthesis (EOS) yield from aqueous fluoride. Compound [18F]16 was obtained with >99% radiochemical purity in a total synthesis time of 3 h. The compound showed good stability in vivo and a fourfold higher uptake in high EGFR expressing A431 tumor xenografts compared to low EGFR expressing HCT116 tumor xenografts. Furthermore, the radiotracer could be visualized in A431 tumor bearing mice by small animal PET imaging. Compound [18F]16 therefore constitutes a promising radiotracer for further evaluation for imaging of EGFR status.
Insights
A novel fluorine-containing compound, [18F]16, shows high affinity for epidermal growth factor receptor (EGFR) and potential for cancer imaging. This radiotracer demonstrated selective uptake in EGFR-expressing tumors, enabling visualization via PET imaging.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Epidermal growth factor receptor (EGFR) is overexpressed in various cancers, making it a target for imaging agents.
- An EGFR-specific imaging agent could aid in evaluating primary tumors and metastases.
Purpose of the Study:
- To design and synthesize a novel fluorine-containing compound for EGFR imaging.
- To evaluate a lead compound, [18F]16, as a potential radioligand for EGFR.
Main Methods:
- Synthesis of fluorine-containing compounds based on a 3-cyanoquinoline core.
- Evaluation of lead compound 16 for EGFR kinase affinity, cellular potency, lipophilicity, and metabolic stability.
- Radiolabeling of compound [18F]16 using 'click' chemistry and assessment of its purity and yield.
- In vivo evaluation in tumor xenografts and small animal PET imaging.
Main Results:
- Lead compound 16 exhibited high affinity (IC50=1.81+/-0.18 nM) and cellular potency (IC50=21.97+/-9.06 nM) for EGFR.
- [18F]16 was synthesized with high radiochemical purity (>99%) and yield (37.0+/-3.6%) in 3 hours.
- The radiotracer showed good in vivo stability and fourfold higher uptake in EGFR-high tumors compared to EGFR-low tumors.
- Small animal PET imaging successfully visualized tumors in mice bearing EGFR-expressing xenografts.
Conclusions:
- Compound [18F]16 is a promising radiotracer for imaging EGFR status in cancer.
- The developed radiotracer demonstrated specificity and sensitivity for EGFR-expressing tumors.
- Further evaluation of [18F]16 is warranted for clinical applications in cancer diagnostics.
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