{"doi":"10.2967/jnumed.121.263221","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 (CRPC). Using the zirconium-89 (<sup>89</sup>Zr)-labeled DLL3 targeting antibody SC16 (<sup>89</sup>Zr-DFO-SC16), we have developed a positron emission tomography (PET) agent to non-invasively identify the presence of DLL3-positive NEPC lesions. <b>Methods:</b> qPCR and immunohistochemistry were used to compare relative levels of androgen receptor (AR)-regulated markers and NEPC marker DLL3 in a panel of prostate cancer cell lines. PET imaging with <sup>89</sup>Zr-DFO-SC16, <sup>68</sup>Ga-PSMA-11, and <sup>68</sup>Ga-DOTA-TATE was performed in H660 NEPC xenografted male nude mice. <sup>89</sup>Zr-DFO-SC16 uptake was corroborated by biodistribution studies. <b>Results:</b> In vitro studies demonstrate H660 are positive for DLL3 and negative for AR, prostate-specific antigen (PSA), and prostate-specific membrane antigen (PSMA) both at the transcriptional and translational levels. PET imaging and biodistribution studies confirm <sup>89</sup>Zr-DFO-SC16 uptake is restricted to H660 tumor 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 (<sup>68</sup>Ga-PSMA-11) or somatostatin receptor subtype 2 (SSTR2) (<sup>68</sup>Ga-DOTA-TATE). <b>Conclusion:</b> These studies demonstrate H660 NEPC cells selectively express DLL3 on their cell surface and can be non-invasively identified with <sup>89</sup>Zr-DFO-SC16.","journal":"Journal of Nuclear Medicine","year":2022,"id":241435,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9647,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":870777,"name":"Teja M. Kalidindi","orcid":null,"position":1,"is_corresponding":false},{"id":870778,"name":"Samantha Khitrov","orcid":null,"position":2,"is_corresponding":false},{"id":751471,"name":"Zachary V. Samuels","orcid":"0000-0001-6639-5402","position":3,"is_corresponding":false},{"id":197793,"name":"Goutam Chakraborty","orcid":null,"position":4,"is_corresponding":false},{"id":870779,"name":"Julia A. Gutierrez","orcid":null,"position":5,"is_corresponding":false},{"id":65360,"name":"John T. Poirier","orcid":"0000-0001-9795-5644","position":6,"is_corresponding":false},{"id":1555,"name":"Charles M. Rudin","orcid":"0000-0001-5204-3465","position":7,"is_corresponding":false},{"id":68839,"name":"Yu Chen","orcid":null,"position":8,"is_corresponding":false},{"id":311748,"name":"Michael J. Morris","orcid":"0000-0002-9454-0096","position":9,"is_corresponding":false},{"id":291557,"name":"Nagavarakishore Pillarsetty","orcid":"0000-0002-1750-7436","position":10,"is_corresponding":false},{"id":235762,"name":"Jason S. Lewis","orcid":"0000-0001-7065-4534","position":11,"is_corresponding":false},{"id":751884,"name":"Joshua A. Korsen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:22:56.227656Z","pmid":"35058323","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}