{
  "abstract": "Background Gastric cancer (GC) remains a leading cause of cancer-related morbidity and mortality worldwide. Human epidermal growth factor receptor 2 (HER2), the first target successfully translated into clinical practice for GC, ushered in a new era of precision medicine. While anti-HER2 therapies have demonstrated remarkable efficacy and expanded patient benefits, there is an urgent need for more precise classification and detection methods for HER2 expression. In this study, we employed a phage-yeast tandem screening strategy to identify a cyclic peptide with nanomolar-level affinity for HER2. Serving as a novel targeting ligand, this peptide provides a critical molecular basis for developing radiopharmaceuticals for precise HER2 diagnosis. Its application promises real-time monitoring of HER2 expression in patients, facilitating personalized treatment planning and enhancing the controllability of targeted therapy.Methods The peptide was screened by phage-yeast tandem screening strategy. HQM-5 was synthesized and radiolabeled with 68Ga. The radiochemical purity was measured by radio-HPLC. Then PET/CT imaging was conducted on HER2-positive NCl-N87 tumor-bearing mice, 200 ± 10 μCi per mouse (n=3). An Investigator-Initiated Trial (IIT) was launched to evaluate [68Ga]Ga-HQM-5 in patients with HER2-positive GC. All enrolled patients underwent [68Ga]Ga-HQM-5 PET/CT imaging to assess the tumor-targeting efficacy and safety of the radiotracer.Results [ 68Ga]Ga-HQM-5 exhibited high radiochemical purity and favorable pharmacokinetics, with a tumor uptake of 8.36 %ID/g at 120 minutes post-injection (IDDF2026-ABS-0403 Figure 1(A)). In addition, it demonstrated excellent specificity, prolonged tumor retention, and a favorable safety profile. In the IIT, [68Ga]Ga-HQM-5 effectively delineated both the primary lesions, showing SUVmax values of 4.21, and liver metastases (SUVmax: 5.76), underscoring its potential for accurate lesion detection (IDDF2026-ABS-0403 Figure 1(B)).Conclusions This study developed a novel HER2-targeted cyclic peptide radiopharmaceutical through combined phage and yeast display screening, which exhibits superior binding affinity to all previously reported HER2-targeted peptides. Preclinical studies demonstrated that [ 68Ga]Ga-HQM-5 exhibits excellent tumor specificity, retention, and safety. Crucially, data from IIT confirmed its robust targeting capability in human GC lesions, supporting its clinical application for real-time monitoring and personalized treatment planning in GC patients.Abstract IDDF2026-ABS-0403 Figure 1",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China"
      ],
      "name": "Xueyao Chen"
    },
    {
      "affiliations": [
        "State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China"
      ],
      "name": "Siqi Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China"
      ],
      "name": "Xinkai Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China"
      ],
      "name": "Kuan Hu"
    }
  ],
  "title": "IDDF2026-ABS-0403 De novo discovery of HER2-targeting cyclic peptide for PET/CT diagnosis of gastric cancer",
  "uid": "87a78a0c-c861-5794-9428-e285d457aa97"
}