Delta-Like Ligand 3 Expression and Functional Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms

Area of Science:

• Oncology
• Molecular Imaging
• Cancer Biology

Background:

• Delta-like ligand 3 (DLL3) is a novel target in neuroendocrine cancers.
• DLL3 expression is not well-characterized in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs).

Purpose of the Study:

• To investigate DLL3 expression across gastroenteropancreatic neuroendocrine neoplasms (GEP NENs).
• To assess the feasibility of DLL3-targeted immuno-PET-CT imaging in GEP NENs.

Main Methods:

• DLL3 immunohistochemistry (IHC) was performed on 379 GEP NEN tumor samples.
• [89Zr]Zr-DFO-SC16.56 immuno-PET-CT imaging was conducted in six patients with DLL3-positive GEP NENs.

Main Results:

• DLL3 expression was found in 71% of GEP neuroendocrine carcinomas (NECs) and 40% of grade 3 gastroenteropancreatic neuroendocrine tumors (GEP NETs).
• DLL3 positivity correlated with increased mortality in advanced G3 PanNETs.
• Immuno-PET-CT successfully visualized DLL3-avid lesions in 5/6 patients, including GEP NECs and G3 PanNETs.

Conclusions:

• DLL3 is expressed in a majority of GEP NECs and a subset of high-grade PanNETs.
• DLL3-targeted imaging demonstrates potential for GEP NECs and high-grade PanNETs.
• DLL3 represents a promising therapeutic target for these GEP NEN subtypes.