{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T15:05:32Z","timestamp":1783868732927,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFE0113500"],"award-info":[{"award-number":["2024YFE0113500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472018"],"award-info":[{"award-number":["82472018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["20240484725"],"award-info":[{"award-number":["20240484725"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acidic extracellular pH (pHe), a hallmark of the solid tumor microenvironment, is closely associated with increased tumor malignancy and therapy resistance. However, the real\u2010time, noninvasive visualization of dynamic pHe changes in vivo remains a formidable technical challenge. In this study, we developed a novel small\u2010molecule ratiometric near\u2010infrared fluorescent probe\u00a0\n                    <jats:bold>PSMA\u2010ratio\u2010pH<\/jats:bold>\n                    targeting the prostate\u2010specific membrane antigen (PSMA), designed to enable rapid and precise imaging of prostate cancer\u00a0acidity in living mice. This probe exhibits a p\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>a<\/jats:sub>\n                    of 6.4, a value well\u2010suitable for tumor acidity detection, along with dual near\u2010infrared emission, high sensitivity (1250\u2010fold activation), good reversibility, concentration\u2010independent response, robust photostability, and high selectivity. Cellular experiments confirmed its specific anchoring to PSMA on the cell membrane and reliable sensing of pHe. In mouse models of prostate cancer, the probe achieved rapid tumor targeting and ratiometric acidity imaging within 15 min post intravenous injection owing to favorable pharmacokinetics and high PSMA affinity, and was capable of monitoring dynamic pH changes in tumor acidosis. This research provides a powerful molecular tool for the real\u2010time and precise visualization of tumor microenvironment acidity, holding broad application prospects in cancer diagnosis and treatment evaluation.\n                  <\/jats:p>","DOI":"10.1002\/chem.71411","type":"journal-article","created":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T14:50:52Z","timestamp":1783867852000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Highly Sensitive PSMA\u2010Targeted Ratiometric NIR Probe for Rapid Imaging of Prostate Cancer Acidity in Living Mice"],"prefix":"10.1002","author":[{"given":"Xuekang","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical Imaging Center, The First Affiliated Hospital Jinan University  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiang","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrc1478","article-title":"Why Do Cancers Have High Aerobic Glycolysis","volume":"4","author":"Gatenby R. A.","year":"2004","journal-title":"Nature Reviews Cancer"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"0057","DOI":"10.1038\/s41551-017-0057","article-title":"Successively Activatable Ultrasensitive Probe for Imaging Tumour Acidity and Hypoxia","volume":"1","author":"Zheng X.","year":"2017","journal-title":"Nature Biomedical Engineering"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1038\/s41467-020-16814-4","article-title":"Exploiting Metabolic Acidosis in Solid Cancers Using a Tumor\u2010agnostic pH\u2010activatable Nanoprobe for Fluorescence\u2010guided Surgery","volume":"11","author":"Voskuil F. J.","year":"2020","journal-title":"Nature Communications"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41467-017-00598-1","article-title":"In Vivo Quantitative Imaging of Tumor pH by Nanosonophore Assisted Multispectral Photoacoustic Imaging","volume":"8","author":"Jo J.","year":"2017","journal-title":"Nature Communications"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nmat3819","article-title":"A Nanoparticle\u2010Based Strategy for the Imaging of a Broad Range of Tumours by Nonlinear Amplification of Microenvironment Signals","volume":"13","author":"Wang Y.","year":"2013","journal-title":"Nature Materials"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/nnano.2016.72","article-title":"A pH\u2010activatable Nanoparticle With Signal\u2010Amplification Capabilities for Non\u2010Invasive Imaging of Tumour Malignancy","volume":"11","author":"Mi P.","year":"2016","journal-title":"Nature Nanotechnology"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the Origin of Cancer Cells","volume":"123","author":"Warburg O.","year":"1956","journal-title":"Science"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.semcancer.2008.03.011","article-title":"Adaptation to Hypoxia and Acidosis in Carcinogenesis and Tumor Progression","volume":"18","author":"Fang J. S.","year":"2008","journal-title":"Seminars in Cancer Biology"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nrc3110","article-title":"Dysregulated pH: A Perfect Storm for Cancer Progression","volume":"11","author":"Webb B. A.","year":"2011","journal-title":"Nature Reviews Cancer"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1158\/0008-5472.CAN-12-2796","article-title":"Acidity Generated by the Tumor Microenvironment Drives Local Invasion","volume":"73","author":"Estrella V.","year":"2013","journal-title":"Cancer Research"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"5216","DOI":"10.1158\/0008-5472.CAN-05-4193","article-title":"Acid\u2010mediated Tumor Invasion: A Multidisciplinary Study","volume":"66","author":"Gatenby R. A.","year":"2006","journal-title":"Cancer Research"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/1475-2867-13-89","article-title":"Acidic Extracellular Microenvironment and Cancer","volume":"13","author":"Kato Y.","year":"2013","journal-title":"Cancer Cell International"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1054\/drup.2000.0119","article-title":"pH and Drug Resistance in Tumors","volume":"3","author":"Raghunand N.","year":"2000","journal-title":"Drug Resistance Updates"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.semcancer.2016.12.003","article-title":"Value of pH Regulators in the Diagnosis, Prognosis and Treatment of Cancer","volume":"43","author":"Granja S.","year":"2017","journal-title":"Seminars in Cancer Biology"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nrd3554","article-title":"Interfering With pH Regulation in Tumours as a Therapeutic Strategy","volume":"10","author":"Neri D.","year":"2011","journal-title":"Nature Reviews Drug Discovery"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/nature07017","article-title":"Magnetic Resonance Imaging of pH in Vivo Using Hyperpolarized 13C\u2010labelled Bicarbonate","volume":"453","author":"Gallagher F. A.","year":"2008","journal-title":"Nature"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"C195","DOI":"10.1152\/ajpcell.1994.267.1.C195","article-title":"31P\u2010MRS Measurements of Extracellular pH of Tumors Using 3\u2010aminopropylphosphonate","volume":"267","author":"Gillies R. J.","year":"1994","journal-title":"American Journal of Physiology"},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1039\/D1CS00525A","article-title":"Activatable Molecular Probes for Fluorescence\u2010Guided Surgery, Endoscopy and Tissue Biopsy","volume":"51","author":"Zhang Y.","year":"2022","journal-title":"Chemical Society Reviews"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1039\/D1CS00307K","article-title":"Activity\u2010based NIR Fluorescent Probes Based on the Versatile Hemicyanine Scaffold","volume":"51","author":"Li H.","year":"2022","journal-title":"Chemical Society Reviews"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1021\/acs.chemrev.3c00778","article-title":"Theranostic Fluorescent Probes","volume":"124","author":"Sharma A.","year":"2024","journal-title":"Chemical Reviews"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"7140","DOI":"10.1039\/C7CS00862G","article-title":"Recent Progresses in Small\u2010Molecule Enzymatic Fluorescent Probes for Cancer Imaging","volume":"47","author":"Liu H. W.","year":"2018","journal-title":"Chemical Society Reviews"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"6707","DOI":"10.1021\/jacs.4c16074","article-title":"Bioorthogonal Reaction of \u03b2\u2010chloroacroleins With Meta\u2010Aminothiophenol to Develop Near\u2010Infrared Fluorogenic Probes for Simultaneous Two\u2010Color Imaging","volume":"147","author":"Wang L.","year":"2025","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_7_24_1","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202107076","article-title":"A General Approach to Design Dual Ratiometric Fluorescent and Photoacoustic Probes for Quantitatively Visualizing Tumor Hypoxia Levels in Vivo","volume":"61","author":"Zhang S.","year":"2022","journal-title":"Angewandte Chemie International Edition"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202418378","article-title":"NIR\u2010II Fluorescence\/Photoacoustic Dual Ratiometric Probes With Unique Recognition Site for Quantitatively Visualizing H2S2 in Vivo","volume":"64","author":"Hu B.","year":"2025","journal-title":"Angewandte Chemie International Edition"},{"key":"e_1_2_7_26_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.snb.2022.132171","article-title":"Rational Design of Dual Ratiometric Photoacoustic and Fluorescent Probe for Reliable Imaging and Quantitative Detection of Endogenous CO During Drug\u2010induced Liver Injury and Repair","volume":"367","author":"Liu L.","year":"2022","journal-title":"Sensors and Actuators B: Chemical"},{"key":"e_1_2_7_27_1","doi-asserted-by":"crossref","first-page":"5925","DOI":"10.1021\/jacs.8b00277","article-title":"Development of a Series of Practical Fluorescent Chemical Tools to Measure pH Values in Living Samples","volume":"140","author":"Takahashi S.","year":"2018","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","first-page":"5091","DOI":"10.1002\/anie.202012021","article-title":"NIR\u2010II pH Sensor With a FRET Adjustable Transition Point for in Situ Dynamic Tumor Microenvironment Visualization","volume":"60","author":"Zhao M.","year":"2021","journal-title":"Angewandte Chemie International Edition"},{"key":"e_1_2_7_29_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1021\/jacs.7b08900","article-title":"Dual\u2010ratiometric Target\u2010triggered Fluorescent Probe for Simultaneous Quantitative Visualization of Tumor Microenvironment Protease Activity and pH in Vivo","volume":"140","author":"Ma T.","year":"2018","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_7_30_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.snb.2025.138357","article-title":"Tumor\u2010Targeted Ratiometric Fluorescent Gold Nanoclusters for Monitoring Apoptosis and Quantifying pH in Vivo","volume":"444","author":"Zhao Y.","year":"2025","journal-title":"Sensors and Actuators B: Chemical"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/med.21508","article-title":"Targeting Prostate Cancer: Prostate\u2010specific Membrane Antigen Based Diagnosis and Therapy","volume":"39","author":"Wustemann T.","year":"2019","journal-title":"Medical Research Reviews"},{"key":"e_1_2_7_32_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1146\/annurev-med-062117-073027","article-title":"Imaging of Prostate\u2010specific Membrane Antigen With Small\u2010molecule PET Radiotracers","volume":"70","author":"Rowe S. P.","year":"2019","journal-title":"Annual Review of Medicine"},{"key":"e_1_2_7_33_1","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1021\/acs.jmedchem.9b02031","article-title":"(S)\u20103\u2010(Carboxyformamido)\u20102\u2010(3\u2010(carboxymethyl)ureido)Propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging","volume":"63","author":"Duan X.","year":"2020","journal-title":"Journal of Medicinal Chemistry"},{"key":"e_1_2_7_34_1","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1007\/s00259-021-05486-x","article-title":"68Ga\u2010labeled ODAP\u2010Urea\u2010based PSMA Agents in Prostate Cancer: First\u2011in\u2011human Imaging of an Optimized Agent","volume":"49","author":"Duan X.","year":"2022","journal-title":"European Journal of Nuclear Medicine and Molecular Imaging"},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1021\/acs.bioconjchem.9b00758","article-title":"Image\u2010guided Surgery: Are We Getting the Most out of Small\u2010Molecule Prostate\u2010Specific\u2010Membrane\u2010Antigen\u2010Targeted Tracers","volume":"31","author":"Hensbergen A. W.","year":"2020","journal-title":"Bioconjugate Chemistry"},{"key":"e_1_2_7_36_1","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1021\/acs.bioconjchem.1c00435","article-title":"Prostate\u2010Specific Membrane Antigen\u2010targeted Turn\u2010on Probe for Imaging Cargo Release in Prostate Cancer Cells","volume":"32","author":"Olatunji F. P.","year":"2021","journal-title":"Bioconjugate Chemistry"},{"key":"e_1_2_7_37_1","doi-asserted-by":"crossref","first-page":"5460","DOI":"10.1038\/s41467-021-25746-6","article-title":"A Prostate\u2010specific Membrane Antigen Activated Molecular Rotor for Real\u2010Time Fluorescence Imaging","volume":"12","author":"Zhang J.","year":"2021","journal-title":"Nature Communications"},{"key":"e_1_2_7_38_1","doi-asserted-by":"crossref","DOI":"10.1002\/chem.202301105","article-title":"Ligand\u2010directed H2S Probe and Scavenger for Specific Tumor Imaging","volume":"29","author":"Cai X.","year":"2023","journal-title":"Chemistry\u2014A European Journal"},{"key":"e_1_2_7_39_1","doi-asserted-by":"crossref","first-page":"7768","DOI":"10.1021\/acs.chemrev.6b00001","article-title":"Recent Development of Chemosensors Based on Cyanine Platforms","volume":"116","author":"Sun W.","year":"2016","journal-title":"Chemical Reviews"},{"key":"e_1_2_7_40_1","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1039\/b007108k","article-title":"A pH Sensitive Fluorescent Cyanine Dye for Biological Applications","volume":"36","author":"Briggs M. S.","year":"2000","journal-title":"Chemical Communications"},{"key":"e_1_2_7_41_1","doi-asserted-by":"crossref","first-page":"11721","DOI":"10.1039\/C5CC03878B","article-title":"A near\u2010infrared Multifunctional Fluorescent Probe With an Inherent Tumor\u2010Targeting Property for Bioimaging","volume":"51","author":"Zhao X.","year":"2015","journal-title":"Chemical Communications"},{"key":"e_1_2_7_42_1","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.cclet.2017.03.037","article-title":"Two near\u2010infrared Highly Sensitive Cyanine Fluorescent Probes for pH Monitoring","volume":"28","author":"Hou J.\u2010R.","year":"2017","journal-title":"Chinese Chemical Letters"},{"key":"e_1_2_7_43_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1039\/D0SC04408C","article-title":"A pH Reversibly Activatable NIR Photothermal\/Photodynamic\u2010in\u2010one Agent Integrated With Renewable Nanoimplants for Image\u2010Guided Precision Phototherapy","volume":"12","author":"Zhao X.","year":"2021","journal-title":"Chemical Science"},{"key":"e_1_2_7_44_1","doi-asserted-by":"crossref","first-page":"5897","DOI":"10.1021\/acs.analchem.5b00053","article-title":"Fluorescent pH Sensors for Broad\u2010Range pH Measurement Based on a Single Fluorophore","volume":"87","author":"Qi J.","year":"2015","journal-title":"Analytical Chemistry"},{"key":"e_1_2_7_45_1","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s00259-012-2069-0","article-title":"[68Ga]Gallium\u2010Labelled PSMA Ligand as Superior PET Tracer for the Diagnosis of Prostate Cancer","volume":"39","author":"Afshar\u2010Oromieh A.","year":"2012","journal-title":"European Journal of Nuclear Medicine and Molecular Imaging"},{"key":"e_1_2_7_46_1","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1158\/0008-5472.CAN-20-1624","article-title":"Cytoplasmic Localization of Prostate\u2010specific Membrane Antigen Inhibitors May Confer Advantages for Targeted Cancer Therapies","volume":"81","author":"Matthias J.","year":"2021","journal-title":"Cancer Research"},{"key":"e_1_2_7_47_1","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1021\/cr900249z","article-title":"Fluorescent Indicators for Intracellular pH","volume":"110","author":"Han J.","year":"2010","journal-title":"Chemical Reviews"},{"key":"e_1_2_7_48_1","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10855","article-title":"Lysosome Triggered near\u2010infrared Fluorescence Imaging of Cellular Trafficking Processes in Real Time","volume":"7","author":"Grossi M.","year":"2016","journal-title":"Nature Communications"},{"key":"e_1_2_7_49_1","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1158\/0008-5472.CAN-07-5575","article-title":"Bicarbonate Increases Tumor pH and Inhibits Spontaneous Metastases","volume":"69","author":"Robey I. F.","year":"2009","journal-title":"Cancer Research"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.71411","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/chem.71411","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.71411","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T14:50:59Z","timestamp":1783867859000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.71411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,12]]},"references-count":48,"alternative-id":["10.1002\/chem.71411"],"URL":"https:\/\/doi.org\/10.1002\/chem.71411","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,12]]},"assertion":[{"value":"2026-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71411"}}