2023 World Conference on Lung Cancer (Posters)-EP13.06. Radiotheranostics targeting Delta-Like Ligand 3 Expressing Small-Cell Lung Cancers.

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Researchers at Memorial Sloan Kettering and New York University have identified potential radiotheranostic agents for small cell lung cancer (SCLC) that target Delta-Like Ligand 3 (DLL3), a protein expressed on the surface of SCLC cells. DLL3 is known to be involved in the progression and survival of SCLC tumors, making it a promising target for therapeutic intervention.<br /><br />In this study, the researchers screened 100 humanized antibodies to identify those with the highest binding affinity and internalization rates for DLL3. Two lead candidates, mAb1 and mAb2, were selected for further investigation and were labeled with either Zirconium-89 (for immuno-positron emission tomography imaging) or Lutetium-177 (for therapy studies).<br /><br />Results showed that both lead antibodies had efficient radioconjugation with the isotopes, and immunoPET imaging revealed high levels of tumor uptake with low background activity in non-tumor organs. Biodistribution analysis confirmed these findings.<br /><br />In therapeutic studies, mice treated with the radioimmunoconjugates showed prolonged overall survival compared to controls, with durable tumor responses observed. Some mice in the lower dose group initially showed signs of tumor progression but responded well to re-treatment with the same dose.<br /><br />Hematologic suppression was observed following treatment but normalized within three weeks. No significant hepatotoxicity was detected.<br /><br />The researchers concluded that the DLL3-targeting radioimmunoconjugates hold promise as diagnostic tracers, prognostic biomarkers, and therapeutic agents for SCLC patients. Further translation and clinical trials are necessary to validate their efficacy and safety.<br /><br />This study highlights the potential of using DLL3 expression as a selective target for the development of novel radiotheranostic agents in the management of small cell lung cancer.

Asset Subtitle

Salomon Tendler

Meta Tag

Speaker Salomon Tendler

Topic SCLC & Neuroendocrine Tumors: Preclinical

Keywords

radiotheranostic agents

small cell lung cancer

DLL3

protein

immunoPET imaging

therapeutic studies

tumor responses

hematologic suppression

diagnostic tracers

clinical trials