{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:22:33Z","timestamp":1788355353418,"version":"build-2803163510"},"reference-count":29,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T00:00:00Z","timestamp":1565222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100011272","name":"European Commission","doi-asserted-by":"publisher","award":["602923"],"award-info":[{"award-number":["602923"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Maximal resection of intrinsic brain tumors is a major prognostic factor for survival. Real-time intraoperative imaging tools, including ultrasound (US), are crucial for maximal resection of such tumors. Microbubbles (MBs) are clinically used in daily practice as a contrast agent for ultrasound and can be further developed to serve combined therapeutic and diagnostic purposes. To achieve this goal, we have developed novel MBs conjugated to specific ligands to receptors which are overexpressed in brain tumors. These MBs are designed to target a tumor tissue, visualize it, and deliver therapeutic molecules into it. The objective of this study was to assess the biodistribution of the test items: We used MBs labeled with indocyanine green (MB-ICG) for visualization and MBs conjugated to a cyclic molecule containing the tripeptide Arg-Gly-Asp (RGD) labeled with ICG (MB-RGD-ICG) to target brain tumor integrins as the therapeutic tools. Male Sprague Dawley rats received a single dose of each MB preparation. The identification of the MB in various organs was monitored by fluorescence microscopy in anesthetized animals as well as real-time US for brain imaging. Equally sized control groups under identical conditions were used in this study. One control group was used to establish fluorescence background conditions (ICG), and two control groups were used to test autofluorescence from the test items (MBs and MB-RGD). ICG with or without MBs (naked or RGD-modified) was detected in the brain vasculature and also in other organs. The pattern, duration, and intensity of the fluorescence signal could not be differentiated between animals treated with ICG alone and animals treated with microbubbles MBs-ICG or MBs-RGD-ICG. Following MB injection, either naked or combined with RGD, there was a sharp rise in the Doppler signal within seconds of injection in the brain. The signal was mainly located at the choroid plexus, septum pellucidum, and the meninges of the brain. The signal subsided within a few minutes. Injection of saline or ICG alone to respective animals did not result in a similar raised signal. Following a single intravenous administration of MB-ICG and MB-RGD-ICG to rats, the MBs were found to be effectively present in the brain.<\/jats:p>","DOI":"10.1021\/acsomega.9b01544","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T10:46:27Z","timestamp":1565261187000},"page":"13371-13381","source":"Crossref","is-referenced-by-count":14,"title":["In Vivo Biodistribution of Engineered\nLipid Microbubbles in Rodents"],"prefix":"10.1021","volume":"4","author":[{"given":"Letizia","family":"Oddo","sequence":"first","affiliation":[{"name":"Universita\u0301 degli Studi di Roma Tor Vergata , , ,","place":["Roma, Italy, 00133"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3051-3811","authenticated-orcid":true,"given":"Gaio","family":"Paradossi","sequence":"additional","affiliation":[{"name":"Universita\u0301 degli Studi di Roma Tor Vergata , , ,","place":["Roma, Italy, 00133"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Cerroni","sequence":"additional","affiliation":[{"name":"Universita\u0301 degli Studi di Roma Tor Vergata , , ,","place":["Roma, Italy, 00133"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmit","family":"Ben-Harush","sequence":"additional","affiliation":[{"name":"Tel-Aviv University , , ,","place":["Tel-Aviv, Israel, 6997801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eti","family":"Ariel","sequence":"additional","affiliation":[{"name":"Tel-Aviv University , , ,","place":["Tel-Aviv, Israel, 6997801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Meco","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta , , ,","place":["Milan, Italy, 20133"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Ram","sequence":"additional","affiliation":[{"name":"Tel-Aviv University , , ,","place":["Tel-Aviv, Israel, 6997801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-375X","authenticated-orcid":true,"given":"Rachel","family":"Grossman","sequence":"additional","affiliation":[{"name":"Tel-Aviv University , , ,","place":["Tel-Aviv, Israel, 6997801"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,8,8]]},"reference":[{"key":"2026090209100612600_cit1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nec.2018.08.010","article-title":"Epidemiology and\nMolecular Epidemiology","volume":"30","author":"Bauchet","year":"2019","journal-title":"Neurosurg. 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Oncol."},{"key":"2026090209100612600_cit5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.addr.2013.11.013","article-title":"Recent advances in molecular, multimodal and theranostic\nultrasound imaging","volume":"72","author":"Kiessling","year":"2014","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026090209100612600_cit6","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1038\/bjc.2013.218","article-title":"Integrin \u03b13\nis overexpressed in glioma stem-like cells and promotes invasion","volume":"108","author":"Nakada","year":"2013","journal-title":"Br. J. Cancer"},{"key":"2026090209100612600_cit7","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s40477-014-0111-8","article-title":"Fusion imaging for\nintra-operative ultrasound-based navigation in neurosurgery","volume":"17","author":"Prada","year":"2014","journal-title":"J. Ultrasound"},{"key":"2026090209100612600_cit8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3171\/2011.2.JNS10998","article-title":"An extent of resection threshold\nfor newly diagnosed glioblastomas","volume":"115","author":"Sanai","year":"2011","journal-title":"J. Neurosurg."},{"key":"2026090209100612600_cit9","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/S1470-2045(11)70196-6","article-title":"Intraoperative MRI guidance and extent of resection\nin glioma surgery: a randomised, controlled trial","volume":"12","author":"Senft","year":"2011","journal-title":"Lancet Oncol."},{"key":"2026090209100612600_cit10","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/S1470-2045(06)70665-9","article-title":"Fluorescence-guided\nsurgery with 5-aminolevulinic acid for resection of malignant glioma:\na randomised controlled multicentre phase III trial","volume":"7","author":"Stummer","year":"2006","journal-title":"Lancet Oncol."},{"key":"2026090209100612600_cit11","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.nec.2018.08.012","article-title":"Surgical Adjuncts to Increase the Extent of Resection","volume":"30","author":"Hollon","year":"2019","journal-title":"Neurosurg. Clin. N. 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Radiat.\nBiol."},{"key":"2026090209100612600_cit19","doi-asserted-by":"publisher","first-page":"5526","DOI":"10.1021\/acsomega.8b03161","article-title":"In Vivo Toxicity Study of Engineered Lipid Microbubbles\nin Rodents","volume":"4","author":"Paradossi","year":"2019","journal-title":"ACS Omega"},{"key":"2026090209100612600_cit20","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1148\/radiol.2491072050","article-title":"Targeted microbubbles for imaging\ntumor angiogenesis: assessment of whole-body biodistribution with\ndynamic micro-PET in mice","volume":"249","author":"Willmann","year":"2008","journal-title":"Radiology"},{"key":"2026090209100612600_cit21","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S0039-6257(00)00123-5","article-title":"Fluorescence properties\nand metabolic features of indocyanine green (ICG) as related to angiography","volume":"45","author":"Desmettre","year":"2000","journal-title":"Surv. 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Echocardiogr."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.9b01544","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/4\/8\/13371\/67756620\/acsomega.9b01544.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/4\/8\/13371\/67756620\/acsomega.9b01544.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:10:13Z","timestamp":1788354613000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/4\/8\/13371\/614664\/In-Vivo-Biodistribution-of-Engineered-Lipid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,8]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8,8]]},"published-print":{"date-parts":[[2019,8,20]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.9b01544","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,8]]}}}