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A Novel Dual-labeled Peptide for Multimodal Imaging of EGFR with L858R Mutation
Myoung Hyoun Kim1, Seul-Gi Kim2, Dae-Weung Kim1,2
1Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.
Background:
The development of molecular imaging agents targeting epidermal growth factor receptor (EGFR) with L858R mutation may help with the selection of non-small cell lung carcinoma (NSCLCL) patients who may benefit from EFGR tyrosine kinase inhibitor (TKI) therapy.
Objective:
In this study, we developed 99mTc STHHYYP-GHEG-ECGK-tetramethylrhodamine (STHHYYP-ECGK-TAMRA) to target EGFR with L858R mutation in NSCLC tumors and verified its probability as a molecular imaging agent.
Methods:
Fmoc solid-phase peptide synthesis was used to synthesize STHHYYP-ECGKTAMRA. 99mTc labelled STHHYYP-ECGK-TAMRA was prepared. Gamma imaging, fluorescent imaging and biodistribution were performed in murine models bearing NCI-H1975 and NCI-H1650 tumors.
Results:
The binding affinity value (Kd) of 99mTc STHHYYP-ECGK-TAMRA was estimated to be 130.6 ± 29.2 nM in NCI-H1975 cells. The gamma camera images showed a substantial uptake of 99mTc STHHYYP-ECGK-TAMRA in the NCI-H1975 tumor. The % injected dose/gram of the NCI-H1975 tumor tissue was 2.77 ± 0.70 and 3.48 ± 1.01 at 1 and 3 h, respectively.
Conclusion:
Specific binding of 99mTc STHHYYP-ECGK-TAMRA to L858R-mutated EGFRpositive NCI-H1975 cells and tumors was demonstrated in in vivo and in vitro studies. The results suggest that 99mTc STHHYYP-ECGK-TAMRA is a good candidate agent for dualmodality imaging targeting EGFR with L858R mutation.
Insights
A new molecular imaging agent, 99mTc STHHYYP-ECGK-TAMRA, specifically targets the L858R mutation in epidermal growth factor receptor (EGFR) in non-small cell lung cancer. This agent shows promise for selecting patients eligible for EGFR tyrosine kinase inhibitor therapy.
Area of Science:
- Oncology
- Molecular Imaging
- Radiochemistry
Background:
- Targeting the epidermal growth factor receptor (EGFR) with the L858R mutation is crucial for selecting non-small cell lung cancer (NSCLC) patients for EGFR tyrosine kinase inhibitor (TKI) therapy.
- Development of specific molecular imaging agents can aid in identifying patients who will benefit from TKI treatment.
Purpose of the Study:
- To develop and validate 99mTc STHHYYP-ECGK-TAMRA as a molecular imaging agent targeting EGFR with the L858R mutation in NSCLC.
- To assess the agent's potential for dual-modality imaging in NSCLC.
Main Methods:
- Synthesis of 99mTc STHHYYP-ECGK-TAMRA using Fmoc solid-phase peptide synthesis.
- Radiolabeling of the synthesized peptide with 99mTc.
- Evaluation of the agent in murine models with NCI-H1975 and NCI-H1650 tumors using gamma and fluorescent imaging, along with biodistribution studies.
Main Results:
- The binding affinity (Kd) of 99mTc STHHYYP-ECGK-TAMRA to NCI-H1975 cells was determined to be 130.6 ± 29.2 nM.
- Gamma imaging demonstrated significant uptake of the agent in NCI-H1975 tumors.
- Biodistribution studies showed tumor uptake of 2.77 ± 0.70% injected dose/gram at 1 hour and 3.48 ± 1.01% at 3 hours in NCI-H1975 tumors.
Conclusions:
- In vitro and in vivo studies confirmed the specific binding of 99mTc STHHYYP-ECGK-TAMRA to L858R-mutated EGFR-positive NCI-H1975 cells and tumors.
- The agent shows potential as a dual-modality imaging agent for targeting EGFR with the L858R mutation in NSCLC.
