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Advances in Delta-like Ligand 3-Targeted Diagnosis and Treatment
Chunxu Cao1, Huirong Nie1, Jingxuan Zhu1
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Abstract:
Neuroendocrine neoplasms (NENs) are rare clinical entities that have long posed significant challenges in diagnosis and treatment due to their high histological heterogeneity, a scarcity of effective therapeutic targets, and consequently, limited treatment options. Delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch signaling pathway, plays a crucial role in neuroendocrine tumors and is highly expressed in malignancies such as small-cell lung cancer and small-cell neuroendocrine prostate cancer. With the continuous advancement of DLL3-targeted technologies in recent years, an increasing number of novel DLL3-targeted agents have emerged, offering diverse antibody and ligand platforms for both ImmunoPET imaging and targeted radionuclide therapy (TRT) in nuclear medicine. Meanwhile, DLL3 ImmunoPET imaging enables noninvasive molecular imaging-based stratification of patients with high DLL3 expression. The two modalities are mutually reinforcing and hold promise for advancing the precision diagnosis and clinical translation of DLL3-targeted strategies in NENs. This review summarizes recent key advancements in DLL3-targeted nuclear medicine and discusses future directions for DLL3 ImmunoPET imaging and TRT.
Insights
New nuclear medicine techniques targeting Delta-like ligand 3 (DLL3) show promise for diagnosing and treating neuroendocrine neoplasms (NENs). DLL3 ImmunoPET imaging and targeted radionuclide therapy (TRT) offer improved precision for these rare cancers.
Area of Science:
- Nuclear medicine
- Oncology
- Molecular imaging
Background:
- Neuroendocrine neoplasms (NENs) present diagnostic and therapeutic challenges due to heterogeneity and limited targets.
- Delta-like ligand 3 (DLL3) is highly expressed in neuroendocrine tumors, including small-cell lung and prostate cancers.
- DLL3 is a crucial target for novel therapeutic strategies in NENs.
Purpose of the Study:
- To review recent advancements in DLL3-targeted nuclear medicine for NENs.
- To discuss future directions for DLL3 ImmunoPET imaging and targeted radionuclide therapy (TRT).
Main Methods:
- Review of emerging DLL3-targeted agents and technologies.
- Analysis of antibody and ligand platforms for ImmunoPET imaging and TRT.
- Evaluation of DLL3 ImmunoPET for patient stratification.
Main Results:
- Advancements in DLL3-targeted technologies have led to novel agents for ImmunoPET imaging and TRT.
- DLL3 ImmunoPET enables noninvasive stratification of patients based on DLL3 expression.
- DLL3-targeted modalities are mutually reinforcing for precision diagnosis and treatment.
Conclusions:
- DLL3-targeted nuclear medicine strategies hold significant promise for NENs.
- ImmunoPET imaging and TRT offer a pathway for precision diagnosis and treatment translation.
- Further research into DLL3-targeted approaches is crucial for advancing NEN care.
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