{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T02:05:16Z","timestamp":1785377116204,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2025,10]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Tumor hypoxia and proliferation are independent predictors of poor prognosis in glioblastoma and WHO grade 4 IDH\u2010mutant astrocytoma, and are closely linked and can synergistically contribute to local recurrence (LR) and poor overall survival (OS). These two hallmarks can be imaged using FMISO and FLT PET, but only on different days due to the PET intrinsic limitation, which jeopardizes the clinical feasibility and accuracy of multi\u2010parametric studies.<\/jats:p>\n <\/jats:sec>\n \n Purpose<\/jats:title>\n In this study, we assess the feasibility of dual\u2010[FMISO+FLT]\u2010PET in a cohort of patients with glioblastoma and WHO grade 4 IDH\u2010mutant astrocytoma.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Eight patients underwent 90\u00a0min dynamic PET (dynPET) with staggered FMISO\/FLT injections followed by two 10\u00a0min scans at 120 and 180\u00a0min post\u2010FMISO injection, respectively. The target volume (TV) was delineated on the 180\u2010min imageset. The FMISO input function (IF) was derived from dynPET images of the carotids using the first 50\u00a0min, and then extrapolated to the rest of dynPET using a 3\u2010exp fit. The IF\n FLT<\/jats:sub>\n was deduced by subtracting the IF\n FMISO<\/jats:sub>\n from IF\n FMISO+FLT<\/jats:sub>\n over the range\u00a0>\u00a050\u00a0min. The FMISO and FLT kinetic rate constants (KRCs) of the TV and cerebellar cortex (reference tissue) were estimated using kinetic modeling (KM) with a parallel dual\u20101\u2010tissue\u20102\u2010compartment model.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Seven out of eight patients with a total of 13 lesions completed the study. All lesions were [FMISO+FLT]\u2010avid at 180\u00a0min post\u2010FMISO injection with a mean SUVR of 1.72 (range:1.26\u20133.23). IDH\u2010mutant WHO grade 4 astrocytomas showed reduced tumor hypoxia. Mean lesion KRCs were K\n 1\u2010FMISO\u00a0<\/jats:sub>\n =\u00a00.18\u00a0mL\/cc\/min (range:0.042\u20130.432), k\n i\u2010FMISO\u00a0<\/jats:sub>\n =\u00a00.011\u00a0min\n \u22121<\/jats:sup>\n (range:0.00\u20130.039), K\n 1\u2010FLT\u00a0<\/jats:sub>\n =\u00a00.103\u00a0mL\/cc\/min (range: 0.004\u20130.357), and K\n i\u2010FLT\u00a0<\/jats:sub>\n =\u00a00.014\u00a0mL\/min\/g (range: 0.00\u20130.062). Cerebellar cortex KRCs were K\n 1\u2010FMISO\u00a0<\/jats:sub>\n =\u00a00.098\u00a0mL\/cc\/min (range:0.055\u20130.225), k\n i\u2010FMISO\u00a0<\/jats:sub>\n =\u00a00.008\u00a0min\n \u22121<\/jats:sup>\n (range:0.002\u20130.014), K\n 1\u2010FLT\u00a0<\/jats:sub>\n =\u00a00.089\u00a0mL\/cc\/min (range: 0.001\u20130.299), and K\n i\u2010FLT\u00a0<\/jats:sub>\n =\u00a00.003\u00a0mL\/min\/g (range:0.00\u20130.007). Lesion perfusion and hypoxia were inversely correlated (\n R<\/jats:italic>\n \u00a0=\u00a00.99).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Dual\u2010[FMISO+FLT]\u2010PET can provide detailed characterization of tumor microenvironment and interaction of multiple hallmarks that yield radio\u2010resistance. This can improve the accuracy of image\u2010guided radiosurgery and radiotherapy, thereby improving clinical outcomes in patients with glioblastoma and IDH\u2010mutant WHO grade 4 astrocytoma.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mp.18124","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T07:35:06Z","timestamp":1759908906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dual\u2010[\n 18<\/sup>\n FMISO +\n 18<\/sup>\n FLT] PET\/CT and MRI imaging in glioblastoma"],"prefix":"10.1002","volume":"52","author":[{"given":"Sadek A.","family":"Nehmeh","sequence":"first","affiliation":[{"name":"Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Cui","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College New York New York 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