{"doi":"10.1007/s00259-024-06722-w","title":"Imaging CAR-NK cells targeted to HER2 ovarian cancer with human sodium-iodide symporter-based positron emission tomography","abstract":"Abstract Chimeric antigen receptor (CAR) cell therapies utilize CARs to redirect immune cells towards cancer cells expressing specific antigens like human epidermal growth factor receptor 2 (HER2). Despite their potential, CAR T cell therapies exhibit variable response rates and adverse effects in some patients. Non-invasive molecular imaging can aid in predicting patient outcomes by tracking infused cells post-administration. CAR-T cells are typically autologous, increasing manufacturing complexity and costs. An alternative approach involves developing CAR natural killer (CAR-NK) cells as an off-the-shelf allogeneic product. In this study, we engineered HER2-targeted CAR-NK cells co-expressing the positron emission tomography (PET) reporter gene human sodium-iodide symporter (NIS) and assessed their therapeutic efficacy and PET imaging capability in a HER2 ovarian cancer mouse model. NK-92 cells were genetically modified to express a HER2-targeted CAR, the bioluminescence imaging reporter Antares, and NIS. HER2-expressing ovarian cancer cells were engineered to express the bioluminescence reporter Firefly luciferase (Fluc). Co-culture experiments demonstrated significantly enhanced cytotoxicity of CAR-NK cells compared to naive NK cells. In vivo studies involving mice with Fluc-expressing tumors revealed that those treated with CAR-NK cells exhibited reduced tumor burden and prolonged survival compared to controls. Longitudinal bioluminescence imaging demonstrated stable signals from CAR-NK cells over time. PET imaging using the NIS-targeted tracer 18F-tetrafluoroborate ([ 18 F]TFB) showed significantly higher PET signals in mice treated with NIS-expressing CAR-NK cells. Overall, our study showcases the therapeutic potential of HER2-targeted CAR-NK cells in an aggressive ovarian cancer model and underscores the feasibility of using human-derived PET reporter gene imaging to monitor these cells non-invasively in patients.","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2024,"id":438330,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.946,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":485012,"name":"Ying Xia","orcid":"0000-0001-9532-9527","position":1,"is_corresponding":false},{"id":1248133,"name":"John J. Kelly","orcid":"0000-0002-3626-8629","position":2,"is_corresponding":false},{"id":1248134,"name":"Rafael E. Sanchez‐Pupo","orcid":"0000-0002-6970-2137","position":3,"is_corresponding":false},{"id":826656,"name":"Francisco M. Martínez","orcid":"0000-0001-6623-8423","position":4,"is_corresponding":false},{"id":1248135,"name":"Matthew S. Fox","orcid":"0000-0002-5121-4661","position":5,"is_corresponding":false},{"id":1248136,"name":"Jonathan D. Thiessen","orcid":"0000-0001-6132-3020","position":6,"is_corresponding":false},{"id":512065,"name":"Justin W. Hicks","orcid":"0000-0003-0269-9364","position":7,"is_corresponding":false},{"id":1059397,"name":"Timothy J. Scholl","orcid":"0000-0002-0807-363X","position":8,"is_corresponding":false},{"id":630570,"name":"John A. Ronald","orcid":"0000-0003-3665-173X","position":9,"is_corresponding":false},{"id":1248132,"name":"Nourhan Shalaby","orcid":"0000-0001-9264-7191","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:00:38.888629Z","pmid":"38722382","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":[]}