{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:15:29Z","timestamp":1789766129645,"version":"4.0.1"},"reference-count":29,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T00:00:00Z","timestamp":1687132800000},"content-version":"unspecified","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-CA139579"],"award-info":[{"award-number":["R01-CA139579"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,5,21]]},"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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 (<jats:sup>19<\/jats:sup>F) magnetic resonance spectroscopy (MRS) of the liver was used to non-invasively infer the ACF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2009hours of culture, followed by a wash step. At 22 days after intravenous infusion of TILs, quantitative single-voxel liver <jats:sup>19<\/jats:sup>F MRS was performed in vivo using a 3T MRI system. From these data, we model the apparent ACF of the initial cell inoculant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We show that it is feasible to PFC-label ~7\u00d710<jats:sup>10<\/jats:sup> TILs (F-TILs) in a single batch in a clinical cell processing facility, while maintaining &gt;90%\u2009cell viability and standard flow cytometry-based release criteria for phenotype and function. Based on quantitative in vivo <jats:sup>19<\/jats:sup>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-007015","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T01:05:10Z","timestamp":1687223110000},"page":"e007015","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"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"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-9304","authenticated-orcid":false,"given":"Eric T","family":"Ahrens","sequence":"first","affiliation":[{"name":"Department of Radiology, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke M","family":"Helfer","sequence":"additional","affiliation":[{"name":"Celsense, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F","family":"O\u2019Hanlon","sequence":"additional","affiliation":[{"name":"Lot 49 Consulting, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanne R","family":"Lister","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie L","family":"Bykowski","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of California San Diego, La Jolla, California, 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