Synapse - Molecular imaging of neuroendocrine prostate cancer by targeting delta-like ligand 3

Molecular imaging of neuroendocrine prostate cancer by targeting delta-like ligand 3 Journal Article

Authors:	Korsen, J. A.; Kalidindi, T. M.; Khitrov, S.; Samuels, Z. V.; Chakraborty, G.; Gutierrez, J. A.; Poirier, J. T.; Rudin, C. M.; Chen, Y.; Morris, M. J.; Pillarsetty, N.; Lewis, J. S.
Article Title:	Molecular imaging of neuroendocrine prostate cancer by targeting delta-like ligand 3
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-desferriox-amine [DFO]-SC16), we have developed a PET agent to noninvasively identify the presence of DLL3-positive NEPC lesions. Methods: Quan-titative 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 transcrip-tional 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.<comment>Superscript/Subscript Available</comment
Journal Title:	Journal of Nuclear Medicine
Volume:	63
Issue:	9
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2022-09-01
Start Page:	1401
End Page:	1407
Language:	English
ACCESSION:	BCI:BCI202200819932
DOI:	10.2967/jnumed.121.263221
PROVIDER:	biosis
PMCID:	PMC9454466
PUBMED:	35058323
Notes:	Article -- Source: Biosis