{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:55:38Z","timestamp":1782280538022,"version":"3.54.5"},"posted":{"date-parts":[[2025,5,10]]},"group-title":"Bioengineering","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Health","award":["R21-CA262736"],"award-info":[{"award-number":["R21-CA262736"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  CAR-T cell therapy has led to remarkable advances in the outcomes of patients with acute lymphoblastic leukemia (ALL), B cell lymphomas, and multiple myeloma. Given these successes in hematologic malignancies, extensive efforts are now focused on developing CAR-T cell therapies for the treatment of solid tumors. The treatment of solid tumors poses significant hurdles with cell trafficking that is necessary to achieve efficacy and minimize off-tumor side effects. The development of simple, safe and inexpensive modalities to track CAR-T cell distribution in humans could provide critical insights to facilitate the development of improved CAR-T products for solid tumors. Here we demonstrate a strategy to monitor CAR-T cells\n                  <jats:italic>in vivo<\/jats:italic>\n                  using ultrasound imaging and nanobubble (NB) labeled cells. NBs are ultrasound contrast agents composed of a lipid shell and a C\n                  <jats:sub>4<\/jats:sub>\n                  F\n                  <jats:sub>10<\/jats:sub>\n                  gas core that can be efficiently internalized into cells. This approach enables us to image the CAR-T cells using nonlinear contrast-enhanced ultrasound (CEUS). Utilizing this method, we found that CAR-T cells can be visualized after injection into both tumor bearing and non-tumor bearing mice. In summary, our ultrasound-based tracking approach can effectively monitor the trafficking of CAR-T cells\n                  <jats:italic>in vivo<\/jats:italic>\n                  , offering a valuable new strategy that can further enable the development of new CAR-T products and strategies to modulate cell trafficking.\n                <\/jats:p>","DOI":"10.1101\/2025.05.06.651695","type":"posted-content","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T22:00:11Z","timestamp":1746914411000},"source":"Crossref","is-referenced-by-count":2,"title":["In vivo tracking of CAR-T cells in tumors via nanobubble-based contrast enhanced ultrasound"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7248-9532","authenticated-orcid":false,"given":"Dorian","family":"Durig","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4276-487X","authenticated-orcid":false,"given":"Jude","family":"Franklin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7856-0484","authenticated-orcid":false,"given":"Reshani","family":"Perera","sequence":"additional","affiliation":[{"name":"Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3655-8279","authenticated-orcid":false,"given":"Zachary","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio 44106, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hosahalli","family":"Vasanna","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio 44106, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9994-8293","authenticated-orcid":false,"given":"Michael C.","family":"Kolios","sequence":"additional","affiliation":[{"name":"Department of Physics Toronto Metropolitan University, Toronto, Ontario, M5B 2K3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-1178","authenticated-orcid":false,"given":"David","family":"Wald","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio 44106, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3913-7066","authenticated-orcid":false,"given":"Agata A.","family":"Exner","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States"},{"name":"Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041121163080000_2025.05.06.651695v1.1","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2023.1188049"},{"key":"2026041121163080000_2025.05.06.651695v1.2","unstructured":"2024 Biological License Application Approvals | FDA. https:\/\/www.fda.gov\/vaccines-blood-biologics\/development-approval-process-cber\/2024-biological-license-application-approvals, (accessed August 2024)"},{"key":"2026041121163080000_2025.05.06.651695v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00832-4"},{"key":"2026041121163080000_2025.05.06.651695v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00459-7"},{"key":"2026041121163080000_2025.05.06.651695v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/9781394180486.ch25"},{"key":"2026041121163080000_2025.05.06.651695v1.6","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003212"},{"key":"2026041121163080000_2025.05.06.651695v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/IRD3.28"},{"key":"2026041121163080000_2025.05.06.651695v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-00511-5"},{"key":"2026041121163080000_2025.05.06.651695v1.9","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-021-01672-3"},{"key":"2026041121163080000_2025.05.06.651695v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0889-6"},{"key":"2026041121163080000_2025.05.06.651695v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2021.03.003"},{"key":"2026041121163080000_2025.05.06.651695v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.10.007"},{"key":"2026041121163080000_2025.05.06.651695v1.13","doi-asserted-by":"publisher","DOI":"10.1080\/13645700801969873"},{"key":"2026041121163080000_2025.05.06.651695v1.14","doi-asserted-by":"publisher","DOI":"10.1080\/14653240802165699"},{"key":"2026041121163080000_2025.05.06.651695v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cocis.2021.101463"},{"key":"2026041121163080000_2025.05.06.651695v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.07.532"},{"key":"2026041121163080000_2025.05.06.651695v1.17","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002735"},{"key":"2026041121163080000_2025.05.06.651695v1.18","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0364-2_13"},{"key":"2026041121163080000_2025.05.06.651695v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.03.020"},{"key":"2026041121163080000_2025.05.06.651695v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.07.058"},{"key":"2026041121163080000_2025.05.06.651695v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2008.03.005"},{"key":"2026041121163080000_2025.05.06.651695v1.22","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12100964"},{"key":"2026041121163080000_2025.05.06.651695v1.23","doi-asserted-by":"publisher","DOI":"10.1021\/acsanm.8b00063"},{"key":"2026041121163080000_2025.05.06.651695v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2020.102213"},{"key":"2026041121163080000_2025.05.06.651695v1.25","doi-asserted-by":"publisher","DOI":"10.7150\/ntno.64735"},{"key":"2026041121163080000_2025.05.06.651695v1.26","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2023.1200310"},{"key":"2026041121163080000_2025.05.06.651695v1.27","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0405"},{"key":"2026041121163080000_2025.05.06.651695v1.28","doi-asserted-by":"publisher","DOI":"10.1182\/BLOOD-2023-185590"},{"key":"2026041121163080000_2025.05.06.651695v1.29","doi-asserted-by":"publisher","DOI":"10.1039\/c9nr04828f"},{"key":"2026041121163080000_2025.05.06.651695v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.08.023"},{"key":"2026041121163080000_2025.05.06.651695v1.31","doi-asserted-by":"publisher","DOI":"10.1109\/58.896136"},{"key":"2026041121163080000_2025.05.06.651695v1.32","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2024.3364076"},{"key":"2026041121163080000_2025.05.06.651695v1.33","doi-asserted-by":"crossref","unstructured":"Needles A , Coulthard T , Theodoropoulos C , Foster S. VisualSonics White Paper: Nonlinear Contrast Agent Imaging with a High Frequency Linear Array Based System VSI White Paper: Nonlinear Contrast Agent Imaging with a High Frequency Linear Array Based System., 2009.","DOI":"10.1109\/ULTSYM.2009.5441633"},{"key":"2026041121163080000_2025.05.06.651695v1.34","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-07934-1"},{"key":"2026041121163080000_2025.05.06.651695v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2021.08.003"},{"key":"2026041121163080000_2025.05.06.651695v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0792-2"},{"key":"2026041121163080000_2025.05.06.651695v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/J.OMTO.2023.04.005"},{"key":"2026041121163080000_2025.05.06.651695v1.38","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001626"},{"key":"2026041121163080000_2025.05.06.651695v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.166"},{"key":"2026041121163080000_2025.05.06.651695v1.40","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2024.1407992\/BIBTEX"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.05.06.651695","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:05:10Z","timestamp":1782277510000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.05.06.651695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,10]]},"references-count":40,"URL":"https:\/\/doi.org\/10.1101\/2025.05.06.651695","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1039\/D5NH00708A","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,5,10]]},"subtype":"preprint"}}