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Updated: Mar 25, 2026
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Peptide-Based ROR1-Targeting PET Ligands for Melanoma Tumor Imaging: Design and Preclinical Evaluation
Donglan Huang1, Xingru Long2,3,4, Li Zhong5
1Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P.R. China.
Abstract:
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in multiple cancers while remaining largely absent in adult tissues, which makes it an attractive target for both tumor diagnosis and therapy. To enable noninvasive imaging of ROR1, four peptide-based PET ligands [68Ga]1-4 were rationally designed and evaluated for melanoma imaging. In vitro assays confirmed reasonable ROR1 binding affinity (KD = 481.0 and 44.9 nM, respectively) and specific cellular uptake of [68Ga]2 and [68Ga]3, which are functionalized with serum albumin-binding groups. Notably, microPET/CT imaging and biodistribution studies in B16F10, A375, and SK-MEL-28 tumor-bearing mice demonstrated that [68Ga]2 achieved the most favorable imaging performance, characterized by high tumor accumulation (up to 9.18% ID/g), sustained retention, and a relatively lower nonspecific background signal. These findings highlight [68Ga]2 as a promising candidate for ROR1-targeting PET imaging and underscore the potential of peptide-based ROR1 PET probes for tumor imaging and therapy guidance.
Insights
Researchers developed novel peptide-based PET ligands to image the cancer target Receptor tyrosine kinase-like orphan receptor 1 (ROR1). The ligand [68Ga]2 showed excellent tumor targeting and retention for melanoma imaging.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in various cancers, making it a promising diagnostic and therapeutic target.
- ROR1's absence in most adult tissues enhances its specificity for cancer detection.
- Noninvasive imaging of ROR1 is crucial for guiding cancer therapy.
Purpose of the Study:
- To design and evaluate novel peptide-based positron emission tomography (PET) ligands for noninvasive ROR1 imaging.
- To assess the in vitro and in vivo performance of these ROR1-targeting PET probes, particularly in melanoma models.
- To identify a lead candidate for ROR1-targeted PET imaging and potential therapeutic applications.
Main Methods:
- Rational design of four peptide-based PET ligands ([68Ga]1-4) targeting ROR1.
- In vitro evaluation of ROR1 binding affinity and specific cellular uptake.
- In vivo microPET/CT imaging and biodistribution studies in melanoma xenograft mouse models (B16F10, A375, SK-MEL-28).
Main Results:
- Ligands [68Ga]2 and [68Ga]3, functionalized with serum albumin-binding groups, demonstrated specific cellular uptake and reasonable ROR1 binding affinity (KD = 481.0 and 44.9 nM).
- [68Ga]2 exhibited superior imaging performance in vivo, with high tumor accumulation (up to 9.18% ID/g), sustained retention, and low background signal in multiple melanoma models.
- Biodistribution studies confirmed the tumor-specific accumulation and retention of [68Ga]2.
Conclusions:
- The peptide-based PET ligand [68Ga]2 is a highly promising candidate for noninvasive ROR1-targeted PET imaging of melanoma.
- The developed ROR1 PET probes demonstrate significant potential for tumor imaging and therapy guidance in clinical oncology.
- Serum albumin-binding groups enhance the performance of peptide-based PET ligands for ROR1 imaging.
