{"doi":"10.1136/jitc-2023-007015","title":"Method for estimation of apoptotic cell fraction of cytotherapy using in vivo fluorine-19 magnetic resonance: pilot study in a patient with head and neck carcinoma receiving tumor-infiltrating lymphocytes labeled with perfluorocarbon nanoemulsion","abstract":"Background Adoptive transfer of T cells is a burgeoning cancer therapeutic approach. However, the fate of the cells, once transferred, is most often unknown. We describe the first clinical experience with a non-invasive biomarker to assay the apoptotic cell fraction (ACF) after cell therapy infusion, tested in the setting of head and neck squamous cell carcinoma (HNSCC). A patient with HNSCC received autologous tumor-infiltrating lymphocytes (TILs) labeled with a perfluorocarbon (PFC) nanoemulsion cell tracer. Nanoemulsion, released from apoptotic cells, clears through the reticuloendothelial system, particularly the Kupffer cells of the liver, and fluorine-19 ( 19 F) magnetic resonance spectroscopy (MRS) of the liver was used to non-invasively infer the ACF. Methods Autologous TILs were isolated from a patient in their late 50s with relapsed, refractory human papillomavirus-mediated squamous cell carcinoma of the right tonsil, metastatic to the lung. A lung metastasis was resected for T cell harvest and expansion using a rapid expansion protocol. The expanded TILs were intracellularly labeled with PFC nanoemulsion tracer by coincubation in the final 24 hours of culture, followed by a wash step. At 22 days after intravenous infusion of TILs, quantitative single-voxel liver 19 F MRS was performed in vivo using a 3T MRI system. From these data, we model the apparent ACF of the initial cell inoculant. Results We show that it is feasible to PFC-label ~7×10 10 TILs (F-TILs) in a single batch in a clinical cell processing facility, while maintaining >90% cell viability and standard flow cytometry-based release criteria for phenotype and function. Based on quantitative in vivo 19 F MRS measurements in the liver, we estimate that ~30% cell equivalents of adoptively transferred F-TILs have become apoptotic by 22 days post-transfer. Conclusions Survival of the primary cell therapy product is likely to vary per patient. A non-invasive assay of ACF over time could potentially provide insight into the mechanisms of response and non-response, informing future clinical studies. This information may be useful to developers of cytotherapies and clinicians as it opens an avenue to quantify cellular product survival and engraftment.","journal":"Journal for ImmunoTherapy of Cancer","year":2023,"id":351301,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1095999,"name":"Brooke Helfer","orcid":"0000-0003-1324-3987","position":1,"is_corresponding":false},{"id":1096000,"name":"Charles F. O’Hanlon","orcid":"0000-0002-2689-9638","position":2,"is_corresponding":false},{"id":755459,"name":"Deanne Lister","orcid":null,"position":3,"is_corresponding":false},{"id":1096405,"name":"Julie L Bykowski","orcid":null,"position":4,"is_corresponding":false},{"id":304702,"name":"Karen Messer","orcid":"0000-0002-9298-2413","position":5,"is_corresponding":false},{"id":445125,"name":"Benjamin I. Leach","orcid":"0000-0002-7379-314X","position":6,"is_corresponding":false},{"id":832420,"name":"Jiawen Chen","orcid":"0000-0001-7101-3034","position":7,"is_corresponding":false},{"id":569733,"name":"Hongyan Xu","orcid":"0000-0001-7432-9018","position":8,"is_corresponding":false},{"id":1096001,"name":"Gregory A. Daniels","orcid":"0000-0001-9087-8009","position":9,"is_corresponding":false},{"id":510055,"name":"Ezra E.W. Cohen","orcid":"0000-0002-9872-6242","position":10,"is_corresponding":false},{"id":683521,"name":"Eric T. Ahrens","orcid":"0000-0001-6131-9304","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T01:12:41.740237Z","pmid":"37339797","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":[]}