CEACAM5-Targeted Immuno-PET in Androgen Receptor-Negative Prostate Cancer.

The incidence of androgen receptor (AR)-negative (AR) prostate cancer, including aggressive neuroendocrine prostate cancer (NEPC), has more than doubled in the last decade, but its timely diagnosis is difficult as it lacks typical prostate cancer hallmarks. The carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) has recently been identified as an upregulated surface antigen in NEPC. We developed an immuno-PET agent targeting CEACAM5 and evaluated its ability to delineate AR prostate cancer in vivo.

Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer.

Tumor expression of prostate-specific membrane antigen (PSMA) is lost in 15-20% of men with castration-resistant prostate cancer (CRPC), yet the underlying mechanisms remain poorly defined. In androgen receptor (AR)-positive CRPC, we observed lower PSMA expression in liver lesions versus other sites, suggesting a role of the microenvironment in modulating PSMA. PSMA suppression was associated with promoter histone 3 lysine 27 methylation and higher levels of neutral amino acid transporters, correlating with F-fluciclovine uptake on positron emission tomography imaging.

Delta-like ligand 3-targeted radioimmunotherapy for neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer with limited meaningful treatment options. NEPC lesions uniquely express delta-like ligand 3 (DLL3) on their cell surface. Taking advantage of DLL3 overexpression, we developed and evaluated lutetium-177 (Lu)-labeled DLL3-targeting antibody SC16 (Lu-DTPA-SC16) as a treatment for NEPC.

Molecular Imaging of Neuroendocrine Prostate Cancer by Targeting Delta-Like Ligand 3.

Treatment-induced neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer. Using the Zr-labeled delta-like ligand 3 (DLL3) targeting antibody SC16 (Zr-desferrioxamine [DFO]-SC16), we have developed a PET agent to noninvasively identify the presence of DLL3-positive NEPC lesions. Quantitative polymerase chain reaction and immunohistochemistry were used to compare relative levels of androgen receptor (AR)-regulated markers and the NEPC marker DLL3 in a panel of prostate cancer cell lines.

Radioimmunotherapy Targeting Delta-like Ligand 3 in Small Cell Lung Cancer Exhibits Antitumor Efficacy with Low Toxicity.

Purpose: Small cell lung cancer (SCLC) is an exceptionally lethal form of lung cancer with limited treatment options. Delta-like ligand 3 (DLL3) is an attractive therapeutic target as surface expression is almost exclusive to tumor cells.

Experimental Design: We radiolabeled the anti-DLL3 mAb SC16 with the therapeutic radioisotope, Lutetium-177.