{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:57:36Z","timestamp":1793422656337,"version":"4.5.0"},"reference-count":75,"publisher":"American Chemical Society (ACS)","issue":"32","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ak0101178"],"award-info":[{"award-number":["JP24ak0101178"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP24K09761"],"award-info":[{"award-number":["JP24K09761"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It is important to clarify the pharmacokinetics of mRNA-loaded lipid nanoparticles (mRNA-LNPs), which have attracted attention as new pharmaceutical modalities for vaccines and therapeutic agents against various diseases. Positron emission tomography (PET) is expected to provide data to ensure the pharmacokinetics of mRNA-LNPs early after administration in detail, especially because of its high temporal resolution. In this study, we have developed a method for the preparation of 64Cu-labeled mRNA-LNPs by an approach via hybridization of short oligonucleotides to the 3\u2032 UTR region of mRNA, and conducted PET pharmacokinetic studies in normal and functionally deficient mice after intravenous and intramuscular administration, which mainly yielded the following findings. First, the common composition of mRNA-LNPs showed a clearly separated two-step accumulation process in the liver after intravenous administration in normal mice, indicating the involvement of ApoE in the second step. Second, after intravenous administration, the time to protein corona formation, in which blood proteins bind to mRNA-LNPs, was found to be within 5\u201310 min. Third, liver and spleen clearance was determined using integration plot analysis, and the contribution of hepatocyte uptake via ApoE to hepatic clearance after intravenous administration was approximately twice that of Kupffer cell uptake. Fourth, a comparison with luciferase reporter protein expression suggested that the protein expression ability of hepatocytes taken up via ApoE after intravenous administration and that of antigen-presenting cells transferred to the lymph nodes after intramuscular administration was remarkably high.<\/jats:p>","DOI":"10.1021\/acsami.5c14143","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T06:38:32Z","timestamp":1754289512000},"page":"45625-45639","source":"Crossref","is-referenced-by-count":10,"title":["Positron Emission\nTomography-Based Pharmacokinetics\nof mRNA\u2013Lipid Nanoparticles: A Study Quantifying the ApoE and\nMacrophage Contribution"],"prefix":"10.1021","volume":"17","author":[{"given":"Kohta","family":"Mohri","sequence":"first","affiliation":[{"name":"RIKEN Center for Biosystems Dynamics Research , , 6-7-3 minatojima-minamimachi, Chuo-ku , , ,","place":["Kobe, Hyogo, Japan, 650-0047"]},{"name":"Nagasaki University , , 1-7-1 Sakamoto , , ,","place":["Nagasaki-shi, Nagasaki, Japan, 852-8588"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Tsukuba Research Laboratories, Eisai Co., Ltd. , 5-1-3 Tokodai , , ,","place":["Tsukuba, Ibaraki, Japan, 300-2635"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Warashina","sequence":"additional","affiliation":[{"name":"RIKEN Center for Biosystems Dynamics Research , , 6-7-3 minatojima-minamimachi, Chuo-ku , , ,","place":["Kobe, Hyogo, Japan, 650-0047"]},{"name":"Nagasaki University , , 1-7-1 Sakamoto , , ,","place":["Nagasaki-shi, Nagasaki, Japan, 852-8588"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"RIKEN Center for Biosystems Dynamics Research , , 6-7-3 minatojima-minamimachi, Chuo-ku , , ,","place":["Kobe, Hyogo, Japan, 650-0047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Ren","sequence":"additional","affiliation":[{"name":"RIKEN Center for Biosystems Dynamics Research , , 6-7-3 minatojima-minamimachi, Chuo-ku , , ,","place":["Kobe, Hyogo, Japan, 650-0047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riho","family":"Iida","sequence":"additional","affiliation":[{"name":"Nagasaki University , , 1-7-1 Sakamoto , , ,","place":["Nagasaki-shi, Nagasaki, Japan, 852-8588"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Wada","sequence":"additional","affiliation":[{"name":"RIKEN Center for Biosystems Dynamics Research , , 6-7-3 minatojima-minamimachi, Chuo-ku , , ,","place":["Kobe, Hyogo, Japan, 650-0047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9174-5213","authenticated-orcid":true,"given":"Kazuya","family":"Maeda","sequence":"additional","affiliation":[{"name":"Kitasato University School of Pharmacy , , 5-9-1 Shirokane, Minato-ku , ,","place":["Tokyo, Japan, 108-8641"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyoshi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"RIKEN Center for Biosystems Dynamics Research , , 6-7-3 minatojima-minamimachi, Chuo-ku , , ,","place":["Kobe, Hyogo, Japan, 650-0047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6240-8552","authenticated-orcid":true,"given":"Yuta","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Tsukuba Research Laboratories, Eisai Co., Ltd. , 5-1-3 Tokodai , , ,","place":["Tsukuba, Ibaraki, Japan, 300-2635"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-8783","authenticated-orcid":true,"given":"Hidefumi","family":"Mukai","sequence":"additional","affiliation":[{"name":"RIKEN Center for Biosystems Dynamics Research , , 6-7-3 minatojima-minamimachi, Chuo-ku , , ,","place":["Kobe, Hyogo, Japan, 650-0047"]},{"name":"Nagasaki University , , 1-7-1 Sakamoto , , ,","place":["Nagasaki-shi, Nagasaki, Japan, 852-8588"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"issue":"6","key":"2026080408090730700_cit1","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/s41587-022-01294-2","article-title":"The clinical\nprogress of mRNA vaccines and immunotherapies","volume":"40","author":"Barbier","year":"2022","journal-title":"Nat. Biotechnol."},{"issue":"11","key":"2026080408090730700_cit2","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1038\/s41587-022-01491-z","article-title":"Unlocking\nthe promise of mRNA therapeutics","volume":"40","author":"Rohner","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"2026080408090730700_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120586","article-title":"mRNA-lipid nanoparticle COVID-19\nvaccines: Structure and stability","volume":"601","author":"Schoenmaker","year":"2021","journal-title":"Int. J. Pharm."},{"issue":"5","key":"2026080408090730700_cit4","doi-asserted-by":"publisher","first-page":"719","DOI":"10.3390\/genes13050719","article-title":"mRNA Vaccines:\nWhy Is the Biology of Retroposition Ignored?","volume":"13","author":"Domazet-Los\u030co","year":"2022","journal-title":"Genes"},{"issue":"15","key":"2026080408090730700_cit5","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1056\/NEJMoa2101765","article-title":"BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass\nVaccination Setting","volume":"384","author":"Dagan","year":"2021","journal-title":"N. Engl. J. Med."},{"issue":"20","key":"2026080408090730700_cit6","doi-asserted-by":"publisher","first-page":"2791","DOI":"10.1016\/j.vaccine.2021.02.007","article-title":"A preliminary report of a randomized\ncontrolled phase 2 trial of the safety and immunogenicity of mRNA-1273\nSARS-CoV-2 vaccine","volume":"39","author":"Chu","year":"2021","journal-title":"Vaccine"},{"issue":"25","key":"2026080408090730700_cit7","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1056\/NEJMoa2027906","article-title":"Safety and immunogenicity of Two RNA-Based Covid-19\nVaccine Candidates","volume":"383","author":"Walsh","year":"2022","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"2026080408090730700_cit8","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20210217","article-title":"mRNA nanomedicine:\nDesign and recent applications","volume":"2","author":"Kubiatowicz","year":"2022","journal-title":"Exploration"},{"issue":"51","key":"2026080408090730700_cit9","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202303261","article-title":"Lipid Nanoparticle\n(LNP) Enables\nmRNA Delivery for Cancer Therapy","volume":"35","author":"Zong","year":"2023","journal-title":"Adv. Mater."},{"issue":"27","key":"2026080408090730700_cit10","doi-asserted-by":"publisher","first-page":"17378","DOI":"10.1021\/acsnano.4c02987","article-title":"Emerging mRNA\nTechnology for Liver Disease Therapy","volume":"18","author":"Wang","year":"2024","journal-title":"ACS Nano"},{"issue":"1","key":"2026080408090730700_cit11","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1038\/s41467-020-16248-y","article-title":"Synergistic lipid compositions for\nalbumin receptor mediated delivery of mRNA to the liver","volume":"11","author":"Miao","year":"2022","journal-title":"Nat. Commun."},{"issue":"12","key":"2026080408090730700_cit12","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1038\/s41591-021-01573-6","article-title":"A phase 1\ntrial of lipid-encapsulated mRNA encoding a monoclonal antibody with\nneutralizing activity against Chikungunya virus","volume":"27","author":"August","year":"2021","journal-title":"Nat. Med."},{"issue":"10427","key":"2026080408090730700_cit13","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/S0140-6736(23)02268-7","article-title":"Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab\nversus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942):\na randomised, phase 2b study","volume":"403","author":"Weber","year":"2024","journal-title":"Lancet"},{"issue":"9","key":"2026080408090730700_cit14","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1016\/j.celrep.2018.02.014","article-title":"A single\nadministration of CRISPR\/Cas9 lipid nanoparticles achieves robust\nand persistent in vivo genome editing","volume":"22","author":"Finn","year":"2018","journal-title":"Cell\nRep."},{"issue":"10","key":"2026080408090730700_cit15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2020401118","article-title":"Lipid nanoparticle-mediated\ncodelivery\nof Cas9 mRNA and single-guide RNA achieves liver-specific in vivo\ngenome editing of Angptl3","volume":"118","author":"Qiu","year":"2021","journal-title":"Proc. Natl. Acad.\nSci. U. S. A."},{"issue":"7859","key":"2026080408090730700_cit16","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/s41586-021-03534-y","article-title":"In vivo CRISPR\nbase editing of PCSK9 durably lowers cholesterol in primates","volume":"593","author":"Musunuru","year":"2021","journal-title":"Nature"},{"key":"2026080408090730700_cit17","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2022.100450","article-title":"Recent advances in\nlipid nanoparticles for delivery of nucleic acid, mRNA, and gene editing-based\ntherapeutics","volume":"44","author":"Mukai","year":"2022","journal-title":"Drug Metab. Pharmacokinet."},{"issue":"12","key":"2026080408090730700_cit18","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles\nfor mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"2026080408090730700_cit19","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.omtn.2023.06.023","article-title":"Lipid nanoparticle-targeted\nmRNA formulation as a treatment for ornithine-transcarbamylase deficiency\nmodel mice","volume":"33","author":"Yamazaki","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"2026080408090730700_cit20","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.omtn.2022.09.017","article-title":"Design and\nlyophilization of lipid nanoparticles for mRNA vaccine and its robust\nimmune response in mice and nonhuman primates","volume":"30","author":"Suzuki","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"issue":"3","key":"2026080408090730700_cit21","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.ymthe.2024.01.020","article-title":"Lymph node macrophages\ndrive innate\nimmune responses to enhance the anti-tumor efficacy of mRNA vaccines","volume":"32","author":"Kubara","year":"2024","journal-title":"Mol. Ther."},{"issue":"4","key":"2026080408090730700_cit22","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41565-020-0669-6","article-title":"Selective\norgan targeting (SORT) nanoparticles for tissue-specific mRNA delivery\nand CRISPR-Cas gene editing","volume":"15","author":"Cheng","year":"2020","journal-title":"Nat. Nanotechnol."},{"key":"2026080408090730700_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114236","article-title":"Regulatory guidelines\nand preclinical tools to study the biodistribution of RNA therapeutics","volume":"184","author":"Vervaeke","year":"2022","journal-title":"Adv. Drug Delivery Rev."},{"issue":"52","key":"2026080408090730700_cit24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109256118","article-title":"On the mechanism\nof tissue-specific\nmRNA delivery by selective organ targeting nanoparticles","volume":"118","author":"Dilliard","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026080408090730700_cit25","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.jconrel.2023.07.058","article-title":"The interplay of\nquaternary ammonium\nlipid structure and protein corona on lung-specific mRNA delivery\nby selective organ targeting (SORT) nanoparticles","volume":"361","author":"Dilliard","year":"2023","journal-title":"J. Controlled Release"},{"key":"2026080408090730700_cit26","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1016\/S0959-8049(02)00413-6","article-title":"PET for in vivo\npharmacokinetic and\npharmacodynamic measurements","volume":"38","author":"Gupta","year":"2002","journal-title":"Eur. J. Cancer"},{"key":"2026080408090730700_cit27","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s00228-003-0643-x","article-title":"Positron emission\ntomography microdosing:\na new concept with application in tracer and early clinical drug development","volume":"59","author":"Bergstrom","year":"2003","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"2026080408090730700_cit28","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.addr.2010.09.010","article-title":"Impact of\nmicrodosing clinical study - why necessary\nand how useful?","volume":"63","author":"Sugiyama","year":"2011","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026080408090730700_cit29","doi-asserted-by":"publisher","first-page":"249","DOI":"10.2967\/jnumed.110.081539","article-title":"PET imaging of the\ngastrointestinal absorption of orally administered drugs in conscious\nand anesthetized rats","volume":"52","author":"Yamashita","year":"2011","journal-title":"J. Nucl. Med."},{"key":"2026080408090730700_cit30","doi-asserted-by":"publisher","first-page":"950","DOI":"10.2967\/jnumed.110.083949","article-title":"Developmental\nchanges in Pglycoprotein function in the blood-brain barrier of nonhuman\nprimates: PET study with R-11C-verapamil and 11C-oseltamivir","volume":"52","author":"Takashima","year":"2011","journal-title":"J. Nucl. Med."},{"key":"2026080408090730700_cit31","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.jconrel.2014.02.014","article-title":"Quantitative evaluation\nof the improvement in the pharmacokinetics\nof a nucleic acid drug delivery system by dynamic PET imaging with\n18F-incorporated oligodeoxynucleotides","volume":"180","author":"Mukai","year":"2014","journal-title":"J. Controlled\nRelease"},{"key":"2026080408090730700_cit32","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.nucmedbio.2020.06.007","article-title":"Review: PET imaging with macro- and middle-sized molecular\nprobes","volume":"92","author":"Mukai","year":"2021","journal-title":"Nucl. Med. Biol."},{"issue":"41","key":"2026080408090730700_cit33","doi-asserted-by":"publisher","first-page":"45763","DOI":"10.1021\/acsami.0c11967","article-title":"In Vivo Tracking\nof Fluorinated Polypeptide\nGene Carriers by Positron Emission Tomography Imaging","volume":"12","author":"Wang","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"issue":"10","key":"2026080408090730700_cit34","doi-asserted-by":"publisher","first-page":"5043","DOI":"10.1021\/acs.molpharmaceut.3c00370","article-title":"In Vivo Imaging of [60]Fullerene-Based\nMolecular Spherical Nucleic Acids by Positron Emission Tomography","volume":"20","author":"A\u0308a\u0308rela\u0308","year":"2023","journal-title":"Mol. Pharmaceutics"},{"key":"2026080408090730700_cit35","doi-asserted-by":"publisher","first-page":"48","DOI":"10.26599\/NBE.2024.9290048","article-title":"Radiolabeled tracing\ntechniques Illuminating Blood Pharmacokinetics in Nanomedicine","volume":"16","author":"Zhou","year":"2024","journal-title":"Nano Biomed. Eng."},{"issue":"6","key":"2026080408090730700_cit36","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1248\/cpb.c24-00089","article-title":"Understanding\nthe Manufacturing Process of Lipid Nanoparticles for mRNA Delivery\nUsing Machine Learning","volume":"72","author":"Sato","year":"2024","journal-title":"Chem. Pharm. Bull."},{"key":"2026080408090730700_cit37","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1021\/bc100018n","article-title":"Liposomal Cu-64\nlabeling method using bifunctional chelators: poly(ethylene glycol)\nspacer and chelator effects","volume":"21","author":"Seo","year":"2010","journal-title":"Bioconjugate Chem."},{"issue":"12","key":"2026080408090730700_cit38","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx290","article-title":"Characterizing exogenous mRNA delivery,\ntrafficking,\ncytoplasmic release and RNA-protein correlations at the level of single\ncells","volume":"45","author":"Kirschman","year":"2017","journal-title":"Nucleic Acids Res."},{"issue":"9","key":"2026080408090730700_cit39","doi-asserted-by":"publisher","first-page":"3740","DOI":"10.1111\/cas.15897","article-title":"Novel strategy\nof liver cancer treatment with modified antisense oligonucleotides\ntargeting human vasohibin-2","volume":"114","author":"Horie","year":"2023","journal-title":"Cancer Sci."},{"key":"2026080408090730700_cit40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.121968","article-title":"64Cu-labeling of small extracellular\nvesicle surfaces via a cross-bridged macrocyclic chelator for pharmacokinetic\nstudy by positron emission tomography imaging","volume":"624","author":"Warashina","year":"2022","journal-title":"Int. J. Pharm."},{"issue":"3","key":"2026080408090730700_cit41","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1021\/acs.molpharmaceut.8b01052","article-title":"Improved Immuno-PET Imaging of HER2-Positive Tumors in Mice: Urokinase\nInjection-Triggered Clearance Enhancement of 64Cu-Trastuzumab","volume":"16","author":"Ren","year":"2019","journal-title":"Mol. Pharmaceutics"},{"key":"2026080408090730700_cit42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2022.106339","article-title":"Lasso peptide\nmicrocin J25 variant containing RGD motif as a PET probe for integrin\nav\u00df3 in tumor imaging","volume":"180","author":"Mohri","year":"2023","journal-title":"Eur. J. Pharm. Sci."},{"issue":"1","key":"2026080408090730700_cit43","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.dmpk.2019.12.004","article-title":"Recent progress\nin in vivo phenotyping technologies for better prediction of transporter-mediated\ndrug-drug interactions","volume":"35","author":"Maeda","year":"2020","journal-title":"Drug Metab. Pharmacokinet."},{"issue":"7","key":"2026080408090730700_cit44","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1023\/A:1018943613122","article-title":"Physiological parameters in laboratory animals and\nhumans","volume":"10","author":"Davies","year":"1993","journal-title":"Pharm. Res."},{"issue":"23","key":"2026080408090730700_cit45","doi-asserted-by":"publisher","first-page":"4829","DOI":"10.1002\/ejic.200500579","article-title":"Kinetic\ninertness and electrochemical behavior of copper(II) tetraazamacrocyclic\ncomplexes: possible implications for in vivo stability","volume":"2005","author":"Woodin","year":"2005","journal-title":"Eur. J. Inorg. Chem."},{"key":"2026080408090730700_cit46","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.jconrel.2018.12.006","article-title":"Pharmacokinetic evaluation\nof Liposomal\nnanoparticle-encapsulated nucleic acid drug: A combined study of dynamic\nPET imaging and LC\/MS\/MS analysis","volume":"294","author":"Mukai","year":"2019","journal-title":"J. Controlled\nRelease"},{"issue":"6","key":"2026080408090730700_cit47","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s41589-019-0285-7","article-title":"Macrocyclic\npeptide-based inhibition and imaging of hepatocyte growth factor","volume":"15","author":"Sakai","year":"2019","journal-title":"Nat. Chem. Biol."},{"issue":"4","key":"2026080408090730700_cit48","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1021\/acs.molpharmaceut.2c01020","article-title":"Two-Chain Mature Hepatocyte Growth\nFactor-Specific Positron Emission Tomography Imaging in Tumors Using\n64Cu-Labeled HiP-8, a Nonstandard Macrocyclic Peptide Probe","volume":"20","author":"Warashina","year":"2023","journal-title":"Mol. Pharmaceutics"},{"issue":"11","key":"2026080408090730700_cit49","doi-asserted-by":"publisher","first-page":"4677","DOI":"10.1021\/acs.analchem.1c04778","article-title":"Size and Charge\nCharacterization\nof Lipid Nanoparticles for mRNA Vaccines","volume":"94","author":"Malburet","year":"2022","journal-title":"Anal.\nChem."},{"issue":"4","key":"2026080408090730700_cit50","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1248\/bpb.b21-01016","article-title":"Importance of Process\nParameters\nInfluencing the Mean Diameters of siRNA-Containing Lipid Nanoparticles\n(LNPs) on the in Vitro Activity of Prepared LNPs","volume":"45","author":"Nakamura","year":"2022","journal-title":"Biol. Pharm. Bull."},{"key":"2026080408090730700_cit51","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.jconrel.2024.07.052","article-title":"Physicochemical\nand structural insights into lyophilized mRNA-LNP from lyoprotectant\nand buffer screenings","volume":"373","author":"Fan","year":"2024","journal-title":"J. Controlled Release"},{"issue":"10","key":"2026080408090730700_cit52","doi-asserted-by":"publisher","first-page":"E1941","DOI":"10.1073\/pnas.1619653114","article-title":"Systemic delivery\nof factor IX messenger RNA for protein replacement therapy","volume":"14","author":"Ramaswamy","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"42","key":"2026080408090730700_cit53","doi-asserted-by":"publisher","first-page":"21150","DOI":"10.1073\/pnas.1906182116","article-title":"Lipid nanoparticle-targeted\nmRNA therapy as a treatment for the inherited metabolic liver disorder\narginase deficiency","volume":"116","author":"Truong","year":"2019","journal-title":"Proc. Natl. Acad. Sci.\nU. S. A."},{"issue":"1","key":"2026080408090730700_cit54","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/s41467-021-20903-3","article-title":"Murine liver repair via transient activation of regenerative\npathways in hepatocytes using lipid nanoparticle-complexed nucleoside-modified\nmRNA","volume":"12","author":"Rizvi","year":"2021","journal-title":"Nat. Commun."},{"issue":"5","key":"2026080408090730700_cit55","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41551-019-0378-3","article-title":"Visualization of early events in mRNA vaccine delivery\nin non-human primates via PET-CT and near-infrared imaging","volume":"3","author":"Lindsay","year":"2019","journal-title":"Nat. Biomed. Eng."},{"issue":"12","key":"2026080408090730700_cit56","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2013.66","article-title":"Influence of Polyethylene\nGlycol Lipid Desorption Rates on Pharmacokinetics and Pharmacodynamics\nof siRNA Lipid Nanoparticles","volume":"2","author":"Mui","year":"2013","journal-title":"Mol. Ther. Nucleic\nAcids"},{"issue":"12","key":"2026080408090730700_cit57","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1038\/s41565-019-0591-y","article-title":"The Onpattro story\nand the clinical translation of nanomedicines containing nucleic acid-based\ndrugs","volume":"14","author":"Akinc","year":"2019","journal-title":"Nat. Nanotechnol."},{"key":"2026080408090730700_cit58","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119792","article-title":"PEG shedding-rate-dependent\nblood clearance of PEGylated lipid nanoparticles in mice: Faster PEG\nshedding attenuates anti-PEG IgM production","volume":"588","author":"Suzuki","year":"2020","journal-title":"Int. J. Pharm."},{"issue":"1","key":"2026080408090730700_cit59","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.ijpharm.2016.06.124","article-title":"Structure, activity and uptake mechanism\nof siRNA-lipid\nnanoparticles with an asymmetric ionizable lipid","volume":"510","author":"Suzuki","year":"2016","journal-title":"Int. J. Pharm."},{"issue":"6","key":"2026080408090730700_cit60","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1007\/s13346-023-01291-1","article-title":"Nanoparticles\nlabeled with gamma-emitting\nradioisotopes: an attractive approach for in vivo tracking using SPECT\nimaging","volume":"13","author":"Ahmadi","year":"2023","journal-title":"Drug Delivery Transl. Res."},{"issue":"9","key":"2026080408090730700_cit61","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1021\/acs.bioconjchem.0c00366","article-title":"The Biomolecular\nCorona of Lipid Nanoparticles for Gene Therapy","volume":"31","author":"Francia","year":"2020","journal-title":"Bioconjugate Chem."},{"key":"2026080408090730700_cit62","unstructured":"Palmer, M.; Bhakdi, S.\n          Pfizer mRNA vaccine:\nPharmacokinetics and Toxicity. 2021. https:\/\/doctors4covidethics.org\/wp-content\/uploads\/2021\/07\/Pfizer-pharmacokinetics-and-toxicity.pdf (accessed July 2025)."},{"key":"2026080408090730700_cit63","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jconrel.2015.08.007","article-title":"Expression\nkinetics of nucleoside-modified mRNA delivered in lipid nanoparticles\nto mice by various routes","volume":"217","author":"Pardi","year":"2015","journal-title":"J. Controlled Release"},{"issue":"1\u20132","key":"2026080408090730700_cit64","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S0169-409X(01)00154-5","article-title":"Liposomes to target\nthe lymphatics by subcutaneous administration","volume":"50","author":"Oussoren","year":"2001","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026080408090730700_cit65","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2021.100424","article-title":"Difference in the lipid\nnanoparticle technology employed\nin three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs","volume":"41","author":"Suzuki","year":"2021","journal-title":"Drug Metab. Pharmacokinet."},{"issue":"11","key":"2026080408090730700_cit66","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/nrd4608","article-title":"From sewer to saviour - targeting\nthe lymphatic system to promote drug exposure and activity","volume":"14","author":"Trevaskis","year":"2015","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026080408090730700_cit67","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.addr.2020.10.002","article-title":"Lymph-directed immunotherapy - Harnessing\nendogenous lymphatic distribution pathways for enhanced therapeutic\noutcomes in cancer","volume":"160","author":"Feeney","year":"2020","journal-title":"Adv. Drug Delivery Rev."},{"issue":"3","key":"2026080408090730700_cit68","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1021\/acs.molpharmaceut.9b01182","article-title":"The Effect\nof Size and Charge of Lipid Nanoparticles\nPrepared by Microfluidic Mixing on Their Lymph Node Transitivity and\nDistribution","volume":"17","author":"Nakamura","year":"2020","journal-title":"Mol. Pharmaceutics"},{"issue":"12","key":"2026080408090730700_cit69","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1016\/j.ymthe.2017.08.006","article-title":"Efficient Targeting and Activation of Antigen-Presenting\nCells In Vivo after Modified mRNA Vaccine Administration in Rhesus\nMacaques","volume":"25","author":"Liang","year":"2017","journal-title":"Mol. Ther."},{"issue":"48","key":"2026080408090730700_cit70","doi-asserted-by":"publisher","first-page":"33058","DOI":"10.1021\/acsnano.4c08490","article-title":"Distinct Inflammatory\nPrograms Underlie the Intramuscular\nLipid Nanoparticle Response","volume":"18","author":"Dowell","year":"2024","journal-title":"ACS Nano"},{"key":"2026080408090730700_cit71","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jconrel.2022.11.036","article-title":"siRNA delivery to lymphatic endothelial cells via ApoE-mediated uptake\nby lipid nanoparticles","volume":"353","author":"Sakurai","year":"2023","journal-title":"J. Controlled Release"},{"key":"2026080408090730700_cit72","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.jconrel.2020.08.031","article-title":"The use of\ndesign of experiments with multiple responses\nto determine optimal formulations for in vivo hepatic mRNA delivery","volume":"327","author":"Hashiba","year":"2020","journal-title":"J. Controlled Release"},{"issue":"8","key":"2026080408090730700_cit73","doi-asserted-by":"publisher","first-page":"3876","DOI":"10.1021\/acs.molpharmaceut.2c01024","article-title":"Delivery and\nExpression of mRNA in\nthe Secondary Lymphoid Organs Drive Immune Responses to Lipid Nanoparticle-mRNA\nVaccines after Intramuscular Injection","volume":"20","author":"Takanashi","year":"2023","journal-title":"Mol.\nPharmaceutics"},{"issue":"29","key":"2026080408090730700_cit74","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201700409","article-title":"Protein Corona: Impact\nof Lymph Versus Blood in a Complex In Vitro Environment","volume":"13","author":"Bonvin","year":"2017","journal-title":"Small"},{"key":"2026080408090730700_cit75","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2024.115304","article-title":"Interactions\nbetween nanoparticles and lymphatic systems: Mechanisms and applications\nin drug delivery","volume":"209","author":"Tang","year":"2024","journal-title":"Adv. Drug Delivery Rev."}],"container-title":["ACS Applied Materials &amp;\nInterfaces"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsami.5c14143","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/17\/32\/45625\/66379280\/acsami.5c14143.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/17\/32\/45625\/66379280\/acsami.5c14143.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:09:38Z","timestamp":1785845378000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aamick\/article\/17\/32\/45625\/3639533\/Positron-Emission-Tomography-Based"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,4]]},"references-count":75,"journal-issue":{"issue":"32","published-online":{"date-parts":[[2025,8,4]]},"published-print":{"date-parts":[[2025,8,13]]}},"URL":"https:\/\/doi.org\/10.1021\/acsami.5c14143","relation":{},"ISSN":["1944-8244","1944-8252"],"issn-type":[{"value":"1944-8244","type":"print"},{"value":"1944-8252","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,4]]}}}