Cell Surface Expression and PET Imaging Establish DLL3 as a Clinically Actionable Target in Neuroblastoma
9 affiliations
- 1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York
- 2Department of Radiology, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York
- 3Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York
- 4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- 5Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
- 6Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York
- 7Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- 8Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York; and
- 9Department of Medicine, NYU Grossman School of Medicine, New York, New York
Abstract
In adult neuroendocrine malignancies, including small cell lung cancer, Delta-like ligand 3 (DLL3) is a validated therapeutic target. DLL3 is expressed in neuroblastoma, a pediatric cancer of neuroendocrine origin, but subcellular localization is incompletely defined, limiting clinical translation of DLL3-targeted therapies for neuroblastoma. Methods: DLL3 expression and localization were evaluated in human neuroblastoma tumors and preclinical models using RNA sequencing, immunohistochemistry, and flow cytometry. To assess in vivo tumor accessibility, DLL3-targeted PET imaging with [89Zr]Zr-deferoxamine-SC16.56 was performed in patient-derived xenograft (PDX) models and in 4 patients with neuroblastoma. Results: DLL3 was broadly expressed across neuroblastoma tumor samples and preclinical models. Although immunohistochemistry demonstrated variable protein expression, flow cytometry revealed near-universal DLL3 cell surface localization across clinical samples and PDX models, including tumors with low expression by immunohistochemistry. DLL3-targeted PET imaging demonstrated tumor-specific uptake in PDX models and in 4 patients with relapsed neuroblastoma, confirming in vivo accessibility of DLL3. Conclusion: DLL3 overexpression in neuroblastoma is associated with targetable cell surface localization, supporting DLL3 as a clinically actionable target for imaging and therapeutic strategies.
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BibTeX
@article{aspromonte2026cell,
title = {{Cell Surface Expression and PET Imaging Establish DLL3 as a Clinically Actionable Target in Neuroblastoma}},
author = {Salvatore M. Aspromonte and Tamar Y. Feinberg and Somali Gavane and Candace Parker and Ali Cihan and Daoqi You and Salomon A. Tendler and Jaime Alvarez-Perez and Samantha Brosius and Armaan Siddiquee and Dylan Domenico and Glorymar Ibañez and Emily Stockfisch and James M. Bean and Anne M. Cochrane and Umesh Bhanot and Satish K. Tickoo and Achim Jungbluth and Denise Frosina and Paola Angelini and Neerav Shukla and Serge K. Lyashchenko and John T. Poirier and Heiko Schoder and Charles M. Rudin and Jason S. Lewis and Kevin J. Curran and Anthony Daniyan and Mark P. Dunphy and Julia L. Glade Bender and Shakeel Modak and Filemon S. Dela Cruz and Andrew L. Kung},
journal = {Journal of Nuclear Medicine},
year = {2026},
month = nov,
doi = {10.2967/jnumed.126.272770},
url = {https://doi.org/10.2967/jnumed.126.272770},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cell Surface Expression and PET Imaging Establish DLL3 as a Clinically Actionable Target in Neuroblastoma
AU - Salvatore M. Aspromonte
AU - Tamar Y. Feinberg
AU - Somali Gavane
AU - Candace Parker
AU - Ali Cihan
AU - Daoqi You
AU - Salomon A. Tendler
AU - Jaime Alvarez-Perez
AU - Samantha Brosius
AU - Armaan Siddiquee
AU - Dylan Domenico
AU - Glorymar Ibañez
AU - Emily Stockfisch
AU - James M. Bean
AU - Anne M. Cochrane
AU - Umesh Bhanot
AU - Satish K. Tickoo
AU - Achim Jungbluth
AU - Denise Frosina
AU - Paola Angelini
AU - Neerav Shukla
AU - Serge K. Lyashchenko
AU - John T. Poirier
AU - Heiko Schoder
AU - Charles M. Rudin
AU - Jason S. Lewis
AU - Kevin J. Curran
AU - Anthony Daniyan
AU - Mark P. Dunphy
AU - Julia L. Glade Bender
AU - Shakeel Modak
AU - Filemon S. Dela Cruz
AU - Andrew L. Kung
PY - 2026
DA - 2026/11/03
JO - Journal of Nuclear Medicine
DO - 10.2967/jnumed.126.272770
UR - https://doi.org/10.2967/jnumed.126.272770
AB - In adult neuroendocrine malignancies, including small cell lung cancer, Delta-like ligand 3 (DLL3) is a validated therapeutic target. DLL3 is expressed in neuroblastoma, a pediatric cancer of neuroendocrine origin, but subcellular localization is incompletely defined, limiting clinical translation of DLL3-targeted therapies for neuroblastoma. Methods: DLL3 expression and localization were evaluated in human neuroblastoma tumors and preclinical models using RNA sequencing, immunohistochemistry, and flow cytometry. To assess in vivo tumor accessibility, DLL3-targeted PET imaging with [89Zr]Zr-deferoxamine-SC16.56 was performed in patient-derived xenograft (PDX) models and in 4 patients with neuroblastoma. Results: DLL3 was broadly expressed across neuroblastoma tumor samples and preclinical models. Although immunohistochemistry demonstrated variable protein expression, flow cytometry revealed near-universal DLL3 cell surface localization across clinical samples and PDX models, including tumors with low expression by immunohistochemistry. DLL3-targeted PET imaging demonstrated tumor-specific uptake in PDX models and in 4 patients with relapsed neuroblastoma, confirming in vivo accessibility of DLL3. Conclusion: DLL3 overexpression in neuroblastoma is associated with targetable cell surface localization, supporting DLL3 as a clinically actionable target for imaging and therapeutic strategies.
SN - 0161-5505
SN - 1535-5667
ER -