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Updated: Apr 26, 2026
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Development of [18F]afatinib as new TKI-PET tracer for EGFR positive tumors
Paul Slobbe1, Albert D Windhorst2, Marijke Stigter-van Walsum3
1Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Introduction:
Afatinib is an irreversible ErbB family blocker that was approved for the treatment of EGFR mutated non-small cell lung cancer in 2013. Positron emission tomography (PET) with fluorine-18 labeled afatinib provides a means to obtain improved understanding of afatinib tumor disposition in vivo. PET imaging with [(18)F]afatinib may also provide a method to select treatment responsive patients. The aim of this study was to label afatinib with fluorine-18 and evaluate its potential as TKI-PET tracer in tumor bearing mice.
Methods:
A radiochemically novel coupling, using peptide coupling reagent BOP, was explored and optimized to synthesize [(18)F]afatinib, followed by a metabolite analysis and biodistribution studies in two clinically relevant lung cancer cell lines, xenografted in nude mice.
Results:
A reliable [(18)F]afatinib radiosynthesis was developed and the tracer could be produced in yields of 17.0 ± 2.5% calculated from [(18)F]F(-) and >98% purity. The identity of the product was confirmed by co-injection on HPLC with non-labeled afatinib. Metabolite analysis revealed a moderate rate of metabolism, with >80% intact tracer in plasma at 45 min p.i. Biodistribution studies revealed rapid tumor accumulation and good retention for a period of at least 2 hours, while background tissues showed rapid clearance of the tracer.
Conclusion:
We have developed a method to synthesize [(18)F]afatinib and related fluorine-18 labeled 4-anilinoquinazolines. [(18)F]Afatinib showed good stability in vivo, justifying further evaluation as a TKI-PET tracer.
Insights
Researchers developed a novel fluorine-18 labeled afatinib ([18F]afatinib) tracer for Positron Emission Tomography (PET) imaging. This tracer demonstrates excellent tumor uptake and retention in mice, showing potential for personalized cancer treatment selection.
Area of Science:
- Nuclear Medicine
- Radiochemistry
- Oncology
Background:
- Afatinib is an approved irreversible ErbB family blocker for EGFR-mutated non-small cell lung cancer.
- Positron Emission Tomography (PET) with radiolabeled tracers offers insights into drug disposition.
- Fluorine-18 labeled afatinib ([18F]afatinib) PET imaging could aid in patient selection for afatinib therapy.
Purpose of the Study:
- To synthesize and characterize [18F]afatinib.
- To evaluate [18F]afatinib as a potential tracer for tyrosine kinase inhibitor (TKI) Positron Emission Tomography (PET) in tumor-bearing mice.
Main Methods:
- Radiosynthesis of [18F]afatinib utilizing a novel peptide coupling reagent (BOP).
- Metabolite analysis in plasma.
- Biodistribution studies in nude mice bearing lung cancer xenografts.
Main Results:
- Reliable radiosynthesis yielding [18F]afatinib with 17.0 ± 2.5% yield and >98% purity.
- High metabolic stability with >80% intact tracer in plasma at 45 minutes post-injection.
- Rapid and significant tumor accumulation with good retention for over 2 hours, contrasted by rapid clearance from background tissues.
Conclusions:
- A method for synthesizing [18F]afatinib and related compounds was successfully developed.
- [18F]Afatinib demonstrated favorable in vivo stability and tumor targeting properties.
- Further evaluation of [18F]afatinib as a TKI-PET tracer is warranted.
