PT  - JOURNAL ARTICLE
AU  - Korsen, Joshua A.
AU  - Kalidindi, Teja M.
AU  - Khitrov, Samantha
AU  - Samuels, Zachary V.
AU  - Chakraborty, Goutam
AU  - Gutierrez, Julia A.
AU  - Poirier, John T.
AU  - Rudin, Charles M.
AU  - Chen, Yu
AU  - Morris, Michael J.
AU  - Pillarsetty, Nagavarakishore
AU  - Lewis, Jason S.
TI  - Molecular Imaging of Neuroendocrine Prostate Cancer by Targeting Delta-Like Ligand 3
AID  - 10.2967/jnumed.121.263221
DP  - 2022 Sep 01
TA  - Journal of Nuclear Medicine
PG  - 1401--1407
VI  - 63
IP  - 9
4099  - http://jnm.snmjournals.org/content/63/9/1401.short
4100  - http://jnm.snmjournals.org/content/63/9/1401.full
SO  - J Nucl Med2022 Sep 01; 63
AB  - 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.