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Updated: Jun 19, 2025
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Development and biological evaluation of 68Ga-labeled peptides for potential application in HER2-positive colorectal
Jinglin Zhang1, Yixiang Lin1, Jingyue Gao1
1Key Laboratory for Experimental Teratology of the Ministry of Education and Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Abstract:
Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world. Human epidermal growth factor receptor 2 (HER2) is a promising target for the diagnosis and treatment of CRC. In this study, we aimed to design, synthesize and label peptide-based positron emission tomography (PET) tracers targeting HER2-positive CRC, namely [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02. The results show that [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02 possessed hydrophilicity, rapid pharmacokinetic properties and excellent stabilities. [68Ga]Ga-ES-02 demonstrated higher binding affinity (Kd = 24.29 ± 4.95 nM) toward the HER2 in CRC. In HER2-positive HT-29 CRC xenograft mouse model, PET study showed specific tumor uptake after injection of [68Ga]Ga-ES-02 (SUV15min max = 0.87 ± 0.03; SUV30min max = 0.64 ± 0.02). In biodistribution study, the T/M ratios of 68Ga-ES-02 at 30 min after injection reached a maximum of 4.07 ± 0.34. In summary, we successfully synthesized and evaluated two novel peptide-based PET tracers. Our data demonstrate that [68Ga]Ga-ES-01/02 is capable of HER2-positive colorectal cancer, with [68Ga]Ga-ES-02 showing superior imaging effect, enhanced targeting, and increased specificity.
Insights
Two novel peptide-based positron emission tomography (PET) tracers, [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02, were developed for targeting human epidermal growth factor receptor 2 (HER2)-positive colorectal cancer (CRC). [68Ga]Ga-ES-02 demonstrated superior imaging and specificity for HER2-positive CRC.
Area of Science:
- Nuclear Medicine
- Oncology
- Radiopharmaceutical Chemistry
Background:
- Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide.
- Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic and diagnostic target in CRC.
- Development of targeted imaging agents is crucial for early diagnosis and personalized treatment of HER2-positive CRC.
Purpose of the Study:
- To design, synthesize, and radiolabel novel peptide-based positron emission tomography (PET) tracers targeting HER2-positive CRC.
- To evaluate the in vitro and in vivo performance of the developed PET tracers, [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02.
- To compare the targeting efficacy and imaging characteristics of [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02 for HER2-positive CRC.
Main Methods:
- Peptide-based PET tracers ([68Ga]Ga-ES-01 and [68Ga]Ga-ES-02) were synthesized and labeled with Gallium-68.
- In vitro characterization included binding affinity studies towards HER2.
- In vivo evaluation involved PET imaging and biodistribution studies in a HER2-positive HT-29 CRC xenograft mouse model.
Main Results:
- [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02 exhibited favorable hydrophilicity, rapid pharmacokinetics, and excellent stability.
- [68Ga]Ga-ES-02 showed a higher binding affinity (Kd = 24.29 ± 4.95 nM) to HER2 in CRC.
- PET imaging revealed specific tumor uptake of [68Ga]Ga-ES-02 in the xenograft model, with significant tumor-to-mouse ratios (T/M = 4.07 ± 0.34 at 30 min).
Conclusions:
- Two novel peptide-based PET tracers, [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02, were successfully developed and evaluated.
- Both tracers demonstrated potential for imaging HER2-positive colorectal cancer.
- [68Ga]Ga-ES-02 exhibited superior imaging performance, enhanced targeting, and increased specificity, making it a promising candidate for clinical application.
