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Updated: Oct 6, 2025
MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent
Published on: September 3, 2013
Molecular Imaging of Neuroendocrine Prostate Cancer by Targeting Delta-Like Ligand 3
Joshua A Korsen1,2, Teja M Kalidindi1, Samantha Khitrov1
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
Abstract:
Treatment-induced neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer. Using the 89Zr-labeled delta-like ligand 3 (DLL3) targeting antibody SC16 (89Zr-desferrioxamine [DFO]-SC16), we have developed a PET agent to noninvasively identify the presence of DLL3-positive NEPC lesions. Methods: 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. PET imaging with 89Zr-DFO-SC16, 68Ga-PSMA-11, and 68Ga-DOTATATE was performed on H660 NEPC-xenografted male nude mice. 89Zr-DFO-SC16 uptake was corroborated by biodistribution studies. Results: In vitro studies demonstrated that H660 NEPC cells are positive for DLL3 and negative for AR, prostate-specific antigen, and prostate-specific membrane antigen (PSMA) at both the transcriptional and the translational levels. PET imaging and biodistribution studies confirmed that 89Zr-DFO-SC16 uptake is restricted to H660 xenografts, with background uptake in non-NEPC lesions (both AR-dependent and AR-independent). Conversely, H660 xenografts cannot be detected with imaging agents targeting PSMA (68Ga-PSMA-11) or somatostatin receptor subtype 2 (68Ga-DOTATATE). Conclusion: These studies demonstrated that H660 NEPC cells selectively express DLL3 on their cell surface and can be noninvasively identified with 89Zr-DFO-SC16.
Insights
A new PET imaging agent, 89Zr-DFO-SC16, can noninvasively detect neuroendocrine prostate cancer (NEPC) by targeting the DLL3 protein. This agent successfully identified NEPC xenografts that were undetectable by other imaging methods.
Area of Science:
- Oncology
- Nuclear Medicine
- Molecular Imaging
Background:
- Neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer.
- Current imaging methods may not effectively detect NEPC lesions.
Purpose of the Study:
- To develop and evaluate a novel PET imaging agent, 89Zr-DFO-SC16, for noninvasive detection of DLL3-positive NEPC.
Main Methods:
- Quantitative PCR and immunohistochemistry to assess marker expression in prostate cancer cell lines.
- PET imaging in mice using 89Zr-DFO-SC16, 68Ga-PSMA-11, and 68Ga-DOTATATE.
- Biodistribution studies to confirm tracer uptake.
Main Results:
- H660 NEPC cells showed high DLL3 expression and lacked AR, PSA, and PSMA.
- 89Zr-DFO-SC16 PET imaging specifically identified H660 xenografts.
- NEPC xenografts were not detected by PSMA or DOTATATE imaging.
Conclusions:
- H660 NEPC cells selectively express DLL3 on their surface.
- 89Zr-DFO-SC16 is a promising PET agent for noninvasive identification of NEPC.
