{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T06:45:50Z","timestamp":1769237150802,"version":"3.49.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"National Science Foundation and National Institutes of Health","award":["CAREER award #1351992 and R01CA264934."],"award-info":[{"award-number":["CAREER award #1351992 and R01CA264934."]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-32618-2","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T12:53:05Z","timestamp":1767185585000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PISTOL MRI allows noninvasive assessment of changes in tumor oxygenation post hypoxia targeted therapy"],"prefix":"10.1038","volume":"16","author":[{"given":"Shubhangi","family":"Agarwal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lakshmisree","family":"Damodaran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Landon J.","family":"Inge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikram D.","family":"Kodibagkar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"32618_CR1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1259\/0007-1285-52-620-650","volume":"52","author":"JM Brown","year":"1979","unstructured":"Brown, J. M. Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism of reoxygenation. Br. J. Radiol. 52, 650\u2013656 (1979).","journal-title":"Br. J. Radiol."},{"key":"32618_CR2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646\u2013674 (2011).","journal-title":"Cell"},{"key":"32618_CR3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/jnci\/93.4.266","volume":"93","author":"M Hockel","year":"2001","unstructured":"Hockel, M. & Vaupel, P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J. Natl Cancer Inst. 93, 266\u2013276 (2001).","journal-title":"J. Natl Cancer Inst."},{"key":"32618_CR4","first-page":"76","volume":"1866","author":"C Michiels","year":"2016","unstructured":"Michiels, C., Tellier, C. & Feron, O. Cycling hypoxia: A key feature of the tumor microenvironment. Biochim. Biophys. Acta. 1866, 76\u201386 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"32618_CR5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1053\/j.semnuclmed.2014.10.002","volume":"45","author":"PN Span","year":"2015","unstructured":"Span, P. N. & Bussink, J. Biology of hypoxia. Semin Nucl. Med. 45, 101\u2013109 (2015).","journal-title":"Semin Nucl. Med."},{"key":"32618_CR6","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1080\/09553000601002324","volume":"82","author":"JL Tatum","year":"2006","unstructured":"Tatum, J. L. et al. Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy. Int. J. Radiat. Biol. 82, 699\u2013757 (2006).","journal-title":"Int. J. Radiat. Biol."},{"key":"32618_CR7","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/bjc.1955.55","volume":"9","author":"RH Thomlinson","year":"1955","unstructured":"Thomlinson, R. H. & Gray, L. H. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br. J. Cancer. 9, 539\u2013549 (1955).","journal-title":"Br. J. Cancer"},{"key":"32618_CR8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-1-4939-0620-8_3","volume":"812","author":"P Vaupel","year":"2014","unstructured":"Vaupel, P. & Mayer, A. Hypoxia in tumors: pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications. Adv. Exp. Med. Biol. 812, 19\u201324 (2014).","journal-title":"Adv. Exp. Med. Biol."},{"key":"32618_CR9","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/HP.S93413","volume":"3","author":"B Muz","year":"2015","unstructured":"Muz, B., de la Puente, P., Azab, F. & Azab, A. K. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl). 3, 83\u201392 (2015).","journal-title":"Hypoxia (Auckl)"},{"key":"32618_CR10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1126\/science.aaf4405","volume":"352","author":"EB Rankin","year":"2016","unstructured":"Rankin, E. B. & Giaccia, A. J. Hypoxic control of metastasis. Science 352, 175\u2013180 (2016).","journal-title":"Science"},{"key":"32618_CR11","doi-asserted-by":"crossref","first-page":"442","DOI":"10.2174\/156652409788167087","volume":"9","author":"S Rockwell","year":"2009","unstructured":"Rockwell, S., Dobrucki, I. T., Kim, E. Y., Marrison, S. T. & Vu, V. T. Hypoxia and radiation therapy: past history, ongoing research, and future promise. Curr. Mol. Med. 9, 442\u2013458 (2009).","journal-title":"Curr. Mol. Med."},{"key":"32618_CR12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0305-7372(03)00003-3","volume":"29","author":"AM Shannon","year":"2003","unstructured":"Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M. & Toomey, D. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat. Rev. 29, 297\u2013307 (2003).","journal-title":"Cancer Treat. Rev."},{"key":"32618_CR13","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1089\/ars.2013.5378","volume":"21","author":"JC Walsh","year":"2014","unstructured":"Walsh, J. C. et al. The clinical importance of assessing tumor hypoxia: relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid. Redox Signal. 21, 1516\u20131554 (2014).","journal-title":"Antioxid. Redox Signal."},{"key":"32618_CR14","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0360-3016(97)00101-6","volume":"38","author":"DM Brizel","year":"1997","unstructured":"Brizel, D. M., Sibley, G. S., Prosnitz, L. R., Scher, R. L. & Dewhirst, M. W. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int. J. Radiat. Oncol. Biol. Phys. 38, 285\u2013289 (1997).","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"32618_CR15","first-page":"5863","volume":"59","author":"JM Brown","year":"1999","unstructured":"Brown, J. M. The hypoxic cell: a target for selective cancer therapy\u2013eighteenth Bruce F. Cain memorial award lecture. Cancer Res. 59, 5863\u20135870 (1999).","journal-title":"Cancer Res."},{"key":"32618_CR16","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2217\/fon.10.1","volume":"6","author":"WA Denny","year":"2010","unstructured":"Denny, W. A. Hypoxia-activated prodrugs in cancer therapy: progress to the clinic. Future Oncol. 6, 419\u2013428 (2010).","journal-title":"Future Oncol."},{"key":"32618_CR17","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1021\/jm701028q","volume":"51","author":"JX Duan","year":"2008","unstructured":"Duan, J. X. et al. Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs. J. Med. Chem. 51, 2412\u20132420 (2008).","journal-title":"J. Med. Chem."},{"key":"32618_CR18","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/bjc.2016.79","volume":"114","author":"FW Hunter","year":"2016","unstructured":"Hunter, F. W., Wouters, B. G. & Wilson, W. R. Hypoxia-activated prodrugs: paths forward in the era of personalised medicine. Br. J. Cancer. 114, 1071\u20131077 (2016).","journal-title":"Br. J. Cancer"},{"key":"32618_CR19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s10555-007-9059-x","volume":"26","author":"G Melillo","year":"2007","unstructured":"Melillo, G. Targeting hypoxia cell signaling for cancer therapy. Cancer Metastasis Rev. 26, 341\u2013352 (2007).","journal-title":"Cancer Metastasis Rev."},{"key":"32618_CR20","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.biotechadv.2016.04.005","volume":"34","author":"A Patel","year":"2016","unstructured":"Patel, A. & Sant, S. Hypoxic tumor microenvironment: opportunities to develop targeted therapies. Biotechnol. Adv. 34, 803\u2013812 (2016).","journal-title":"Biotechnol. Adv."},{"key":"32618_CR21","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00280-015-2920-7","volume":"77","author":"RM Phillips","year":"2016","unstructured":"Phillips, R. M. Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs. Cancer Chemother. Pharmacol. 77, 441\u2013457 (2016).","journal-title":"Cancer Chemother. Pharmacol."},{"key":"32618_CR22","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.pharmthera.2016.04.009","volume":"164","author":"C Wigerup","year":"2016","unstructured":"Wigerup, C., Pahlman, S. & Bexell, D. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacol. Ther. 164, 152\u2013169 (2016).","journal-title":"Pharmacol. Ther."},{"key":"32618_CR23","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nrc3064","volume":"11","author":"WR Wilson","year":"2011","unstructured":"Wilson, W. R. & Hay, M. P. Targeting hypoxia in cancer therapy. Nat. Rev. Cancer. 11, 393\u2013410 (2011).","journal-title":"Nat. Rev. Cancer"},{"key":"32618_CR24","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/0360-3016(86)90267-1","volume":"12","author":"EM Zeman","year":"1986","unstructured":"Zeman, E. M., Brown, J. M., Lemmon, M. J., Hirst, V. K. & Lee, W. W. SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells. Int. J. Radiat. Oncol. Biol. Phys. 12, 1239\u20131242 (1986).","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"32618_CR25","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0040-4020(01)89952-X","volume":"43","author":"EA Oostveen","year":"1987","unstructured":"Oostveen, E. A. & Speckamp, W. N. Mitomycin Analogs.1. Indoloquinones as (Potential) bisalkylating agents. Tetrahedron 43, 255\u2013262 (1987).","journal-title":"Tetrahedron"},{"key":"32618_CR26","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1158\/1078-0432.CCR-07-0478","volume":"13","author":"AV Patterson","year":"2007","unstructured":"Patterson, A. V. et al. Mechanism of action and preclinical antitumor activity of the novel hypoxia-activated DNA cross-linking agent PR-104. Clin. Cancer Research: Official J. Am. Association Cancer Res. 13, 3922\u20133932 (2007).","journal-title":"Clin. Cancer Research: Official J. Am. Association Cancer Res."},{"key":"32618_CR27","doi-asserted-by":"crossref","first-page":"5118","DOI":"10.1021\/jm800496s","volume":"51","author":"CR Nishida","year":"2008","unstructured":"Nishida, C. R. & de Ortiz, P. R. Reductive heme-dependent activation of the n-oxide prodrug AQ4N by nitric oxide synthase. J. Med. Chem. 51, 5118\u20135120 (2008).","journal-title":"J. Med. Chem."},{"key":"32618_CR28","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1007\/s00280-012-1852-8","volume":"69","author":"Q Liu","year":"2012","unstructured":"Liu, Q. et al. TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules. Cancer Chemother. Pharmacol. 69, 1487\u20131498 (2012).","journal-title":"Cancer Chemother. Pharmacol."},{"issue":"15_Supplement","key":"32618_CR29","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.1158\/1538-7445.AM2015-5358","volume":"75","author":"AV Patterson","year":"2015","unstructured":"Patterson, A. V. et al. The hypoxia-activated EGFR-TKI TH-4000 overcomes erlotinib-resistance in preclinical NSCLC models at plasma levels achieved in a phase 1 clinical trial. Cancer Res. 75 (15_Supplement), 5358 (2015).","journal-title":"Cancer Res."},{"key":"32618_CR30","doi-asserted-by":"crossref","first-page":"e13548","DOI":"10.1200\/jco.2015.33.15_suppl.e13548","volume":"33","author":"AV Patterson","year":"2015","unstructured":"Patterson, A. V. et al. TH-4000, a hypoxia-activated EGFR\/Her2 inhibitor to treat EGFR-TKI resistant T790M-negative NSCLC. J. Clin. Oncol. 33, e13548\u2013e13548 (2015).","journal-title":"J. Clin. Oncol."},{"key":"32618_CR31","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1080\/15384047.2015.1017171","volume":"16","author":"MR Abbattista","year":"2015","unstructured":"Abbattista, M. R. et al. Pre-clinical activity of PR-104 as monotherapy and in combination with Sorafenib in hepatocellular carcinoma. Cancer Biol. Ther. 16, 610\u2013622 (2015).","journal-title":"Cancer Biol. Ther."},{"key":"32618_CR32","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1158\/1078-0432.CCR-14-3378","volume":"22","author":"J Benito","year":"2016","unstructured":"Benito, J. et al. Hypoxia-Activated prodrug TH-302 targets hypoxic bone marrow niches in preclinical leukemia models. Clin. Cancer Research: Official J. Am. Association Cancer Res. 22, 1687\u20131698 (2016).","journal-title":"Clin. Cancer Research: Official J. Am. Association Cancer Res."},{"key":"32618_CR33","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1200\/JCO.2000.18.6.1254","volume":"18","author":"J Del Rowe","year":"2000","unstructured":"Del Rowe, J. et al. Single-arm, open-label phase II study of intravenously administered Tirapazamine and radiation therapy for glioblastoma multiforme. J. Clin. Oncol. 18, 1254\u20131259 (2000).","journal-title":"J. Clin. Oncol."},{"key":"32618_CR34","doi-asserted-by":"crossref","first-page":"927","DOI":"10.3324\/haematol.2014.118455","volume":"100","author":"M Konopleva","year":"2015","unstructured":"Konopleva, M. et al. Phase I\/II study of the hypoxia-activated prodrug PR104 in refractory\/relapsed acute myeloid leukemia and acute lymphoblastic leukemia. Haematologica 100, 927\u2013934 (2015).","journal-title":"Haematologica"},{"key":"32618_CR35","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3109\/02656736.2012.714517","volume":"28","author":"S Masunaga","year":"2012","unstructured":"Masunaga, S. et al. Usefulness of combined treatment with continuous administration of Tirapazamine and mild temperature hyperthermia in gamma-ray irradiation in terms of local tumour response and lung metastatic potential. Int. J. Hyperth. 28, 636\u2013644 (2012).","journal-title":"Int. J. Hyperth."},{"key":"32618_CR36","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1158\/1078-0432.CCR-11-1980","volume":"18","author":"JD Sun","year":"2012","unstructured":"Sun, J. D. et al. Selective tumor hypoxia targeting by hypoxia-activated prodrug TH-302 inhibits tumor growth in preclinical models of cancer. Clin. Cancer Research: Official J. Am. Association Cancer Res. 18, 758\u2013770 (2012).","journal-title":"Clin. Cancer Research: Official J. Am. Association Cancer Res."},{"key":"32618_CR37","first-page":"885","volume":"34","author":"D Groshar","year":"1993","unstructured":"Groshar, D. et al. Imaging tumor hypoxia and tumor perfusion. J. Nucl. Med. 34, 885\u2013888 (1993).","journal-title":"J. Nucl. Med."},{"key":"32618_CR38","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1089\/ars.2013.5759","volume":"21","author":"CT Lee","year":"2014","unstructured":"Lee, C. T., Boss, M. K. & Dewhirst, M. W. Imaging tumor hypoxia to advance radiation oncology. Antioxid. Redox Signal. 21, 313\u2013337 (2014).","journal-title":"Antioxid. Redox Signal."},{"key":"32618_CR39","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.2174\/138161208786404380","volume":"14","author":"H Minn","year":"2008","unstructured":"Minn, H. et al. Imaging of tumor hypoxia to predict treatment sensitivity. Curr. Pharm. Design. 14, 2932\u20132942 (2008).","journal-title":"Curr. Pharm. Design"},{"key":"32618_CR40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/nbm.1558","volume":"24","author":"J Pacheco-Torres","year":"2011","unstructured":"Pacheco-Torres, J., Lopez-Larrubia, P., Ballesteros, P. & Cerdan, S. Imaging tumor hypoxia by magnetic resonance methods. NMR Biomed. 24, 1\u201316 (2011).","journal-title":"NMR Biomed."},{"key":"32618_CR41","first-page":"203","volume":"10","author":"G Reischl","year":"2007","unstructured":"Reischl, G. et al. Imaging of tumor hypoxia with [124I]IAZA in comparison with [18F]FMISO and [18F]FAZA\u2013first small animal PET results. J. Pharm. Pharm. Sciences: Publication Can. Soc. Pharm. Sci. Societe Canadienne des. Sci. Pharmaceutiques. 10, 203\u2013211 (2007).","journal-title":"J. Pharm. Pharm. Sciences: Publication Can. Soc. Pharm. Sci. Societe Canadienne des. Sci. Pharmaceutiques"},{"key":"32618_CR42","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1089\/ars.2014.6155","volume":"22","author":"P Vaupel","year":"2015","unstructured":"Vaupel, P. & Mayer, A. The clinical importance of assessing tumor hypoxia: relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid. Redox Signal. 22, 878\u2013880 (2015).","journal-title":"Antioxid. Redox Signal."},{"key":"32618_CR43","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1002\/mrm.10318","volume":"48","author":"C Baudelet","year":"2002","unstructured":"Baudelet, C. & Gallez, B. How does blood oxygen level-dependent (BOLD) contrast correlate with oxygen partial pressure (pO2) inside tumors? Magn. Reson. Med. 48, 980\u2013986 (2002).","journal-title":"Magn. Reson. Med."},{"key":"32618_CR44","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1002\/jmri.24006","volume":"38","author":"Y Ding","year":"2013","unstructured":"Ding, Y. et al. Simultaneous measurement of tissue oxygen level-dependent (TOLD) and blood oxygenation level-dependent (BOLD) effects in abdominal tissue oxygenation level studies. J. Magn. Reson. Imaging. 38, 1230\u20131236 (2013).","journal-title":"J. Magn. Reson. Imaging"},{"key":"32618_CR45","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1158\/0008-5472.CAN-15-2062","volume":"76","author":"JP O\u2019Connor","year":"2016","unstructured":"O\u2019Connor, J. P. et al. Oxygen-Enhanced MRI accurately Identifies, Quantifies, and maps tumor hypoxia in preclinical cancer models. Cancer Res. 76, 787\u2013795 (2016).","journal-title":"Cancer Res."},{"key":"32618_CR46","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00775-013-1058-5","volume":"19","author":"PK Gulaka","year":"2014","unstructured":"Gulaka, P. K. et al. GdDO3NI, a nitroimidazole-based T1 MRI contrast agent for imaging tumor hypoxia in vivo. J. Biol. Inorg. Chem. 19, 271\u2013279 (2014).","journal-title":"J. Biol. Inorg. Chem."},{"key":"32618_CR47","doi-asserted-by":"crossref","first-page":"9669","DOI":"10.1002\/chem.201200266","volume":"18","author":"FA Rojas-Quijano","year":"2012","unstructured":"Rojas-Quijano, F. A. et al. Synthesis and characterization of a hypoxia-sensitive MRI probe. Chemistry 18, 9669\u20139676 (2012).","journal-title":"Chemistry"},{"key":"32618_CR48","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/(SICI)1099-1492(199605)9:3<125::AID-NBM405>3.0.CO;2-F","volume":"9","author":"RP Mason","year":"1996","unstructured":"Mason, R. P., Rodbumrung, W. & Antich, P. P. Hexafluorobenzene: a sensitive 19F NMR indicator of tumor oxygenation. NMR Biomed. 9, 125\u2013134 (1996).","journal-title":"NMR Biomed."},{"key":"32618_CR49","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/mrm.20826","volume":"55","author":"VD Kodibagkar","year":"2006","unstructured":"Kodibagkar, V. D., Cui, W., Merritt, M. E. & Mason, R. P. Novel 1H NMR approach to quantitative tissue oximetry using hexamethyldisiloxane. Magn. Reson. Med. 55, 743\u2013748 (2006).","journal-title":"Magn. Reson. Med."},{"key":"32618_CR50","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1002\/nbm.1279","volume":"21","author":"VD Kodibagkar","year":"2008","unstructured":"Kodibagkar, V. D., Wang, X., Pacheco-Torres, J., Gulaka, P. & Mason, R. P. Proton imaging of siloxanes to map tissue oxygenation levels (PISTOL): a tool for quantitative tissue oximetry. NMR Biomed. 21, 899\u2013907 (2008).","journal-title":"NMR Biomed."},{"key":"32618_CR51","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/s41598-020-57889-9","volume":"10","author":"S Agarwal","year":"2020","unstructured":"Agarwal, S., Gulaka, P. K., Rastogi, U. & Kodibagkar, V. D. More bullets for PISTOL: linear and Cyclic siloxane reporter probes for quantitative (1)H MR oximetry. Sci. Rep. 10, 1399 (2020).","journal-title":"Sci. Rep."},{"key":"32618_CR52","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/0730-725X(92)90448-9","volume":"10","author":"M Hoehn-Berlage","year":"1992","unstructured":"Hoehn-Berlage, M., Tolxdorff, T., Bockhorst, K., Okada, Y. & Ernestus, R. I. In vivo NMR T2 relaxation of experimental brain tumors in the cat: a multiparameter tissue characterization. Magn. Reson. Imaging. 10, 935\u2013947 (1992).","journal-title":"Magn. Reson. Imaging"},{"key":"32618_CR53","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/S0076-6879(04)86018-X","volume":"386","author":"D Zhao","year":"2004","unstructured":"Zhao, D., Jiang, L. & Mason, R. P. Measuring changes in tumor oxygenation. Methods Enzymol. 386, 378\u2013418 (2004).","journal-title":"Methods Enzymol."},{"key":"32618_CR54","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/mrm.22267","volume":"63","author":"AN Dula","year":"2010","unstructured":"Dula, A. N., Gochberg, D. F., Valentine, H. L., Valentine, W. M. & Does, M. D. Multiexponential T2, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord. Magn. Reson. Med. 63, 902\u2013909 (2010).","journal-title":"Magn. Reson. Med."},{"key":"32618_CR55","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.nicl.2013.06.007","volume":"2","author":"KD Harkins","year":"2013","unstructured":"Harkins, K. D., Valentine, W. M., Gochberg, D. F. & Does, M. D. In-vivo multi-exponential T2, magnetization transfer and quantitative histology in a rat model of intramyelinic edema. Neuroimage Clin. 2, 810\u2013817 (2013).","journal-title":"Neuroimage Clin."},{"key":"32618_CR56","doi-asserted-by":"crossref","first-page":"229","DOI":"10.18383\/j.tom.2016.00259","volume":"2","author":"AM Stokes","year":"2016","unstructured":"Stokes, A. M., Hart, C. P. & Quarles, C. C. Hypoxia imaging with PET correlates with antitumor activity of the Hypoxia-Activated prodrug Evofosfamide (TH-302) in rodent glioma models. Tomography 2, 229\u2013237 (2016).","journal-title":"Tomography"},{"key":"32618_CR57","doi-asserted-by":"crossref","first-page":"e107995","DOI":"10.1371\/journal.pone.0107995","volume":"9","author":"Y Takakusagi","year":"2014","unstructured":"Takakusagi, Y. et al. Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302. PLoS One. 9, e107995 (2014).","journal-title":"PLoS One"},{"key":"32618_CR58","first-page":"1921","volume":"47","author":"MH Cherk","year":"2006","unstructured":"Cherk, M. H. et al. Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET. J. Nucl. Med. 47, 1921\u20131926 (2006).","journal-title":"J. Nucl. Med."},{"key":"32618_CR59","first-page":"106","volume":"46","author":"M Piert","year":"2005","unstructured":"Piert, M. et al. Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J. Nucl. Med. 46, 106\u2013113 (2005).","journal-title":"J. Nucl. Med."},{"key":"32618_CR60","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1158\/1535-7163.MCT-05-0066","volume":"4","author":"B Solomon","year":"2005","unstructured":"Solomon, B. et al. Modulation of intratumoral hypoxia by the epidermal growth factor receptor inhibitor gefitinib detected using small animal PET imaging. Mol. Cancer Ther. 4, 1417\u20131422 (2005).","journal-title":"Mol. Cancer Ther."},{"key":"32618_CR61","first-page":"411","volume":"4","author":"Y Lin","year":"2014","unstructured":"Lin, Y., Wang, X. & Jin, H. EGFR-TKI resistance in NSCLC patients: mechanisms and strategies. Am. J. Cancer Res. 4, 411\u2013435 (2014).","journal-title":"Am. J. Cancer Res."},{"key":"32618_CR62","doi-asserted-by":"crossref","first-page":"e1226","DOI":"10.1371\/journal.pone.0001226","volume":"2","author":"K Choi","year":"2007","unstructured":"Choi, K., Creighton, C. J., Stivers, D., Fujimoto, N. & Kurie, J. M. Transcriptional profiling of non-small cell lung cancer cells with activating EGFR somatic mutations. PLoS One. 2, e1226 (2007).","journal-title":"PLoS One"},{"key":"32618_CR63","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/ijc.1557","volume":"94","author":"NG Anderson","year":"2001","unstructured":"Anderson, N. G., Ahmad, T., Chan, K., Dobson, R. & Bundred, N. J. ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR-positive cancer cell lines with or without erbB2 overexpression. Int. J. Cancer. 94, 774\u2013782 (2001).","journal-title":"Int. J. Cancer"},{"key":"32618_CR64","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrc1367","volume":"4","author":"JM Brown","year":"2004","unstructured":"Brown, J. M. & Wilson, W. R. Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer. 4, 437\u2013447 (2004).","journal-title":"Nat. Rev. Cancer"},{"key":"32618_CR65","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1667\/RR0807.1","volume":"167","author":"WR Wilson","year":"2007","unstructured":"Wilson, W. R. et al. Bystander effects of bioreductive drugs: potential for exploiting pathological tumor hypoxia with Dinitrobenzamide mustards. Radiat. Res. 167, 625\u2013636 (2007).","journal-title":"Radiat. Res."},{"key":"32618_CR66","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1177\/1533034615574386","volume":"15","author":"ND Arvold","year":"2016","unstructured":"Arvold, N. D., Heidari, P., Kunawudhi, A., Sequist, L. V. & Mahmood, U. Tumor hypoxia response after targeted therapy in EGFR-Mutant Non-Small cell lung cancer: proof of concept for FMISO-PET. Technol. Cancer Res. Treat. 15, 234\u2013242 (2016).","journal-title":"Technol. Cancer Res. Treat."},{"key":"32618_CR67","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.ijrobp.2008.11.068","volume":"74","author":"LJ Bains","year":"2009","unstructured":"Bains, L. J., Baker, J. H., Kyle, A. H., Minchinton, A. I. & Reinsberg, S. A. Detecting vascular-targeting effects of the hypoxic cytotoxin Tirapazamine in tumor xenografts using magnetic resonance imaging. Int. J. Radiat. Oncol. Biol. Phys. 74, 957\u2013965 (2009).","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"32618_CR68","doi-asserted-by":"crossref","first-page":"e76832","DOI":"10.1371\/journal.pone.0076832","volume":"8","author":"JH Baker","year":"2013","unstructured":"Baker, J. H. et al. Targeting the tumour vasculature: exploitation of low oxygenation and sensitivity to NOS Inhibition by treatment with a hypoxic cytotoxin. PLoS One. 8, e76832 (2013).","journal-title":"PLoS One"},{"key":"32618_CR69","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.radonc.2006.01.002","volume":"78","author":"LA Huxham","year":"2006","unstructured":"Huxham, L. A., Kyle, A. H., Baker, J. H., McNicol, K. L. & Minchinton, A. I. Tirapazamine causes vascular dysfunction in HCT-116 tumour xenografts. Radiother Oncol. 78, 138\u2013145 (2006).","journal-title":"Radiother Oncol."},{"key":"32618_CR70","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.mvr.2007.09.006","volume":"75","author":"LA Huxham","year":"2008","unstructured":"Huxham, L. A., Kyle, A. H., Baker, J. H., McNicol, K. L. & Minchinton, A. I. Exploring vascular dysfunction caused by Tirapazamine. Microvasc Res. 75, 247\u2013255 (2008).","journal-title":"Microvasc Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32618-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32618-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32618-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T01:04:14Z","timestamp":1769216654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32618-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,31]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["32618"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-32618-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,31]]},"assertion":[{"value":"28 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2877"}}