{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:07:24Z","timestamp":1789117644712,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["1R21DA064871"],"award-info":[{"award-number":["1R21DA064871"]}]},{"name":"National Institute of Health","award":["DP1DA058360"],"award-info":[{"award-number":["DP1DA058360"]}]},{"award":["1R21DA064871"],"award-info":[{"award-number":["1R21DA064871"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DP1DA058360"],"award-info":[{"award-number":["DP1DA058360"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Massachusetts General Brigham"},{"id":[{"id":"https:\/\/ror.org\/04b6nzv94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The David Borsook Project Award for Pain Research\u2013The Cathedral Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Quantitative PET imaging of \u03bc-opioid receptor (MOR) availability and pharmacologic engagement can advance in vivo studies of opioid receptor biology. We previously evaluated a series of 18F-labeled carfentanil analogs and prioritized the regioisomer [18F]fluorocarfentanil ([18F]FCFN) based on favorable brain kinetics, regional distribution, and naloxone-sensitive binding. Here, we provide proof-of-concept evaluation of [18F]FCFN in rhesus macaques to assess its potential for quantitative, pharmacologically responsive MOR PET. Methods: [18F]FCFN was produced by automated radiosynthesis. Dynamic [18F]FCFN PET scans were performed in two rhesus macaques under baseline conditions, after low- (0.005 mg\/kg) and high-dose (0.2 mg\/kg) naloxone pretreatment, and during within-scan intravenous or intranasal naloxone challenge. For arterial input scans, two-tissue compartment modeling with metabolite-corrected arterial input functions was used to estimate total distribution volume (VT). Nondisplaceable binding potential (BPND) was estimated using multilinear reference tissue model 2 with the cerebellum as the candidate reference region. Results: Automated radiosynthesis produced [18F]FCFN in high radiochemical yield and molar activity, enabling low-mass PET injections (0.09\u20130.32 \u03bcg). [18F]FCFN showed rapid brain uptake and MOR-consistent regional distribution, with lowest uptake in the cerebellum. Regional BPND correlated positively with VT at baseline (R2 = 0.983, p &lt; 0.0001) and after high-dose blockade (R2 = 0.522, p &lt; 0.004). Naloxone pretreatment reduced regional BPND in a dose-dependent manner. Within-scan intravenous and intranasal naloxone challenges also produced marked reductions in BPND. Conclusions: [18F]FCFN enables quantitative, pharmacologically sensitive MOR PET imaging in nonhuman primates at low injected masses. Concordant plasma-input and reference-tissue measures, dose-dependent blockade, and proof-of-concept within-scan displacement support its use for measuring MOR availability and dynamic antagonist engagement across administration routes.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091141","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:13:03Z","timestamp":1789031583000},"page":"1141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative \u03bc-Opioid Receptor PET with [18F]FCFN in Nonhuman Primates: Naloxone Blockade and Within-Scan Displacement"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1548-4960","authenticated-orcid":false,"given":"Evan","family":"Gallagher","sequence":"first","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Joseph W.","family":"Downey","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-4583","authenticated-orcid":false,"given":"Chi-Hyeon","family":"Yoo","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Hongping","family":"Deng","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Jessie Fanglu","family":"Fu","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8826-5171","authenticated-orcid":false,"given":"Qikai","family":"Qin","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Irena","family":"Bass","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-8489","authenticated-orcid":false,"given":"Hsiao-Ying","family":"Wey","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Jacob M.","family":"Hooker","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Christin Y.","family":"Sander","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0349-0765","authenticated-orcid":false,"given":"So Jeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neuropharm.2008.07.033","article-title":"Opioid Receptors: From Binding Sites to Visible Molecules in Vivo","volume":"56","author":"Kieffer","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1124\/pr.112.005942","article-title":"Regulation of M-Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance","volume":"65","author":"Williams","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1146\/annurev-neuro-080317-061522","article-title":"Endogenous and Exogenous Opioids in Pain","volume":"41","author":"Corder","year":"2018","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41583-018-0028-x","article-title":"Opioid Receptors: Drivers to Addiction?","volume":"19","author":"Darcq","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/jcbfm.1989.59","article-title":"Multicompartmental Analysis of [11C]-Carfentanil Binding to Opiate Receptors in Humans Measured by Positron Emission Tomography","volume":"9","author":"Frost","year":"1989","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00259-008-0935-6","article-title":"Measurement of Central M-Opioid Receptor Binding in Vivo with PET and [11C]Carfentanil: A Test\u2013Retest Study in Healthy Subjects","volume":"36","author":"Hirvonen","year":"2009","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1126\/science.1060952","article-title":"Regional Mu Opioid Receptor Regulation of Sensory and Affective Dimensions of Pain","volume":"293","author":"Zubieta","year":"2001","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S0304-3959(02)00266-X","article-title":"Pain Activation of Human Supraspinal Opioid Pathways as Demonstrated by [11C]-Carfentanil and Positron Emission Tomography (PET)","volume":"99","author":"Bencherif","year":"2002","journal-title":"Pain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/nm1196-1225","article-title":"Increased Mu Opioid Receptor Binding Detected by PET in Cocaine\u2013Dependent Men Is Associated with Cocaine Craving","volume":"2","author":"Zubieta","year":"1996","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/archpsyc.62.1.57","article-title":"Correlation of Stable Elevations in Striatal \u03bc-Opioid Receptor Availability in Detoxified Alcoholic Patients With Alcohol Craving: A Positron Emission Tomography Study Using Carbon 11\u2013Labeled Carfentanil","volume":"62","author":"Heinz","year":"2005","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/s41386-019-0368-x","article-title":"Intranasal Naloxone Rapidly Occupies Brain Mu-Opioid Receptors in Human Subjects","volume":"44","author":"Johansson","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_12","first-page":"1112","article-title":"[11C]Carfentanil PET Whole-Body Imaging of \u03bc-Opioid Receptors: A First in-Human Study","volume":"66","author":"Dubroff","year":"2025","journal-title":"J. Nucl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16250","DOI":"10.1038\/s41598-024-66144-4","article-title":"Investigation of [11C]Carfentanil for Mu Opioid Receptor Quantification in the Rat Brain","volume":"14","author":"Kelleher","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/jcbfm.1990.90","article-title":"Comparison of [11C]Diprenorphine and [11C]Carfentanil Binding to Opiate Receptors in Humans by Positron Emission Tomography","volume":"10","author":"Frost","year":"1990","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_15","first-page":"1279","article-title":"6-O-(2-[18F]Fluoroethyl)-6-O-Desmethyldiprenorphine ([18F]DPN): Synthesis, Biologic Evaluation, and Comparison with [11C]DPN in Humans","volume":"41","author":"Wester","year":"2000","journal-title":"J. Nucl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117865","DOI":"10.1016\/j.ejmech.2025.117865","article-title":"PET Imaging of the Opioid System Using Radioligands: Synthetic Approaches and Translational Applications","volume":"296","author":"Reale","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1021\/acs.jmedchem.4c02287","article-title":"Selective Mu-Opioid Receptor Imaging Using 18F-Labeled Carfentanils","volume":"68","author":"Lee","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"du Sert, N.P., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0020-7101(93)90049-C","article-title":"Models for Computer Simulation Studies of Input Functions for Tracer Kinetic Modeling with Positron Emission Tomography","volume":"32","author":"Feng","year":"1993","journal-title":"Int. J. Bio-Med. Comput."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7999","DOI":"10.1021\/jm500872p","article-title":"In Vivo Imaging of Histone Deacetylases (HDACs) in the Central Nervous System and Major Peripheral Organs","volume":"57","author":"Wang","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1148\/radiol.2483071927","article-title":"Simultaneous MR\/PET Imaging of the Human Brain: Feasibility Study","volume":"248","author":"Schlemmer","year":"2008","journal-title":"Radiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.2967\/jnumed.118.217901","article-title":"Development of Dedicated Brain PET Imaging Devices: Recent Advances and Future Perspectives","volume":"60","author":"Catana","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.neuroimage.2007.12.025","article-title":"Brain Morphometry with Multiecho MPRAGE","volume":"40","author":"Benner","year":"2008","journal-title":"NeuroImage"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/syn.20062","article-title":"Effect of Amphetamine on [18F]Fallypride in Vivo Binding to D2 Receptors in Striatal and Extrastriatal Regions of the Primate Brain: Single Bolus and Bolus plus Constant Infusion Studies","volume":"54","author":"Slifstein","year":"2004","journal-title":"Synapse"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF01731836","article-title":"Assessing Neuroreceptor Occupancy by Continuous Infusion of Carbon-11 Labeled Radioligands","volume":"23","author":"Kao","year":"1996","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.2967\/jnumed.109.069112","article-title":"Toward Implementing an MRI-Based PET Attenuation-Correction Method for Neurologic Studies on the MR-PET Brain Prototype","volume":"51","author":"Catana","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1148\/radiology.153.1.6089263","article-title":"Simple Proton Spectroscopic Imaging","volume":"153","author":"Dixon","year":"1984","journal-title":"Radiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/jmri.21492","article-title":"Dixon Techniques for Water and Fat Imaging","volume":"28","author":"Ma","year":"2008","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.neuroimage.2012.01.021","article-title":"FreeSurfer","volume":"62","author":"Fischl","year":"2012","journal-title":"NeuroImage"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1002\/(SICI)1522-2594(199912)42:6<1014::AID-MRM4>3.0.CO;2-F","article-title":"Real-Time 3D Image Registration for Functional MRI","volume":"42","author":"Cox","year":"1999","journal-title":"Magn. Reson. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0262-8856(00)00052-4","article-title":"Reconstructing a 3D Structure from Serial Histological Sections","volume":"19","author":"Ourselin","year":"2001","journal-title":"Image Vis. Comput."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"024003","DOI":"10.1117\/1.JMI.1.2.024003","article-title":"Global Image Registration Using a Symmetric Block-Matching Approach","volume":"1","author":"Modat","year":"2014","journal-title":"J. Med. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.neuroimage.2008.10.058","article-title":"A Population-Average MRI-Based Atlas Collection of the Rhesus Macaque","volume":"45","author":"McLaren","year":"2009","journal-title":"NeuroImage"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rohlfing, T., Kroenke, C.D., Sullivan, E.V., Dubach, M.F., Bowden, D.M., Grant, K., and Pfefferbaum, A. (2012). The INIA19 Template and NeuroMaps Atlas for Primate Brain Image Parcellation and Spatial Normalization. Front. Neuroinform., 6.","DOI":"10.3389\/fninf.2012.00027"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1038\/sj.jcbfm.9600493","article-title":"Consensus Nomenclature for in Vivo Imaging of Reversibly Binding Radioligands","volume":"27","author":"Innis","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/00004728-198503000-00001","article-title":"Imaging Opiate Receptors in the Human Brain by Positron Tomography","volume":"9","author":"Frost","year":"1985","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1007\/s00259-024-06746-2","article-title":"Total-Body Imaging of Mu-Opioid Receptors with [11C]Carfentanil in Non-Human Primates","volume":"51","author":"Hsieh","year":"2024","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1097\/01.WCB.0000085441.37552.CA","article-title":"Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain","volume":"23","author":"Ichise","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Herz, A., Akil, H., and Simon, E.J. (1993). Anatomical Distribution of Opioid Receptors in Mammalians: An Overview. Opioids, Springer.","DOI":"10.1007\/978-3-642-77460-7"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0969-8051(02)00411-0","article-title":"Quantification of Brain \u03bc-Opioid Receptors with [11C]Carfentanil: Reference-Tissue Methods","volume":"30","author":"Endres","year":"2003","journal-title":"Nucl. Med. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.pharmthera.2012.03.003","article-title":"Intranasal Drug Delivery: An Efficient and Non-Invasive Route for Systemic Administration: Focus on Opioids","volume":"134","author":"Buenestado","year":"2012","journal-title":"Pharmacol. Ther."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1141\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:24:16Z","timestamp":1789115056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pharmaceutics18091141"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18091141","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]}}}