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

Joshua A. Korsen, Teja M. Kalidindi, Samantha Khitrov, Zachary V. Samuels, Goutam Chakraborty, Julia A. Gutierrez, John T. Poirier, Charles M. Rudin, Yu Chen, Michael J. Morris, Nagavarakishore Pillarsetty, Jason S. Lewis

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish
Pages (from-to)1401-1407
Number of pages7
JournalJournal of Nuclear Medicine
Issue number9
StatePublished - 1 Sep 2022


  • DLL3
  • immuno-PET
  • molecular imaging
  • neuroendocrine prostate cancer


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