{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:06:01Z","timestamp":1790777161144,"version":"4.1.0"},"reference-count":126,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01AA024788"],"award-info":[{"award-number":["K01AA024788"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21EB027872"],"award-info":[{"award-number":["R21EB027872"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG058773"],"award-info":[{"award-number":["R01AG058773"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Glioblastoma multiforme (GBM) is the deadliest type of brain tumor, affecting approximately three in 100,000 adults annually. Positron emission tomography (PET) imaging provides an important non-invasive method of measuring biochemically specific targets at GBM lesions. These powerful data can characterize tumors, predict treatment effectiveness, and monitor treatment. This review will discuss the PET imaging agents that have already been evaluated in GBM patients so far, and new imaging targets with promise for future use. Previously used PET imaging agents include the tracers for markers of proliferation ([11C]methionine; [18F]fluoro-ethyl-L-tyrosine, [18F]Fluorodopa, [18F]fluoro-thymidine, and [18F]clofarabine), hypoxia sensing ([18F]FMISO, [18F]FET-NIM, [18F]EF5, [18F]HX4, and [64Cu]ATSM), and ligands for inflammation. As cancer therapeutics evolve toward personalized medicine and therapies centered on tumor biomarkers, the development of complimentary selective PET agents can dramatically enhance these efforts. Newer biomarkers for GBM PET imaging are discussed, with some already in use for PET imaging other cancers and neurological disorders. These targets include Sigma 1, Sigma 2, programmed death ligand 1, poly-ADP-ribose polymerase, and isocitrate dehydrogenase. For GBM, these imaging agents come with additional considerations such as blood\u2013brain barrier penetration, quantitative modeling approaches, and nonspecific binding.<\/jats:p>","DOI":"10.3390\/molecules25030568","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T09:37:09Z","timestamp":1580204229000},"page":"568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Approaches to PET Imaging of Glioblastoma"],"prefix":"10.3390","volume":"25","author":[{"given":"Lindsey R.","family":"Drake","sequence":"first","affiliation":[{"name":"Yale PET Center, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Department of Radiology and Bioimaging Sciences, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansel T.","family":"Hillmer","sequence":"additional","affiliation":[{"name":"Yale PET Center, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Department of Radiology and Bioimaging Sciences, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-6760","authenticated-orcid":false,"given":"Zhengxin","family":"Cai","sequence":"additional","affiliation":[{"name":"Yale PET Center, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Department of Radiology and Bioimaging Sciences, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,28]]},"reference":[{"key":"ref_1","unstructured":"(2019, November 15). Glioblastoma Multiforme. Available online: https:\/\/www.aans.org\/Patients\/Neurosurgical-Conditions-and-Treatments\/Glioblastoma-Multiforme."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization classification of tumors of the central nervous system: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Amelot, A., De Cremoux, P., Quillien, V., Polivka, M., Adle-Biassette, H., Lehmann-Che, J., Francoise, L., Carpentier, A.F., George, B., and Mandonnet, E. (2015). IDH-mutation is a weak predictor of long-term survival in glioblastoma patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130596"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/BST20180444","article-title":"Glioblastoma heterogeneity and the tumour microenvironment: Implications for preclinical research and development of new treatments","volume":"47","author":"Perrin","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ozdemir-Kaynak, E., Qutub, A.A., and Yesil-Celiktas, O. (2018). Advances in Glioblastoma Multiforme Treatment: New Models for Nanoparticle Therapy. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00170"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"024501","DOI":"10.1117\/1.JMI.6.2.024501","article-title":"Glioma grading using structural magnetic resonance imaging and molecular data","volume":"6","author":"Reza","year":"2019","journal-title":"J. Med. Imaging"},{"key":"ref_7","first-page":"670","article-title":"A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): Nontoxic tracer for rapid tumor detection","volume":"21","author":"Som","year":"1980","journal-title":"J. Nucl Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0020-708X(76)90088-0","article-title":"The preparation of carbon-11-labeled methyl iodide and its use in the synthesis of carbon-11-labeled methyl-L-methionine","volume":"27","author":"Langstrom","year":"1976","journal-title":"Int. J. Appl. Radiat. Isot."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF00253260","article-title":"Labeling and metabolism of methionine-methyl-11C","volume":"1","author":"Comar","year":"1976","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00256026","article-title":"Non selective transport of [11C-methyl]-L-and D-methionine into a malignant glioma","volume":"13","author":"Schober","year":"1987","journal-title":"Eur J. Nucl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11307-007-0115-2","article-title":"11C-L-methionine positron emission tomography in the clinical management of cerebral gliomas","volume":"10","author":"Singhal","year":"2008","journal-title":"Mol. Imaging Biol."},{"key":"ref_12","first-page":"205","article-title":"Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging","volume":"40","author":"Wester","year":"1999","journal-title":"J. Nucl. Med."},{"key":"ref_13","first-page":"1367","article-title":"Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo","volume":"40","author":"Heiss","year":"1999","journal-title":"J. Nucl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00726-014-1863-3","article-title":"System L amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-L-tyrosine (FET)","volume":"47","author":"Habermeier","year":"2015","journal-title":"Amino Acids"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1093\/brain\/awh399","article-title":"O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas","volume":"128","author":"Pauleit","year":"2005","journal-title":"Brain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.2967\/jnumed.109.065664","article-title":"18F-FDOPA: A multiple-target molecule","volume":"50","author":"Minn","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s11060-018-2877-6","article-title":"18F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naive gliomas: A cross-sectional study","volume":"139","author":"Patel","year":"2018","journal-title":"J. Neuro-Oncol."},{"key":"ref_18","first-page":"417","article-title":"High yield synthesis of 6-[18F] fluoro-L-dopa","volume":"27","author":"Chirakal","year":"1986","journal-title":"J. Nucl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mossine, A.V., Tanzey, S.S., Brooks, A.F., Makaravage, K.J., Ichiishi, N., Miller, J.M., Henderson, B.D., Skaddan, M.B., Sanford, M.S., and Scott, P.J.H. (2019). One-pot synthesis of high molar activity 6-[18F]fluoro-L-DOPA by Cu-mediated fluorination of a BPin precursor. Org. Biomol. Chem., Ahead of Print.","DOI":"10.1039\/C9OB01758E"},{"key":"ref_20","first-page":"1210","article-title":"Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells","volume":"43","author":"Rasey","year":"2002","journal-title":"J. Nucl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0969-8051(02)00286-X","article-title":"Basis of FLT as a cell proliferation marker: Comparative uptake studies with [3H] thymidine and [3H] arabinothymidine, and cell-analysis in 22 asynchronously growing tumor cell lines","volume":"29","author":"Toyohara","year":"2002","journal-title":"Nucl. Med. Biol."},{"key":"ref_22","first-page":"3315","article-title":"In vivo validation of 3\u2019deoxy-3\u2019-[18F]fluorothymidine ([18F]FLT) as a proliferation imaging tracer in humans: Correlation of [18F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors","volume":"8","author":"Vesselle","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1007\/s00259-004-1687-6","article-title":"[18F]FLT-PET in oncology: Current status and opportunities","volume":"31","author":"Been","year":"2004","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.2967\/jnumed.112.104729","article-title":"Correlation of 18F-FLT uptake with tumor grade and Ki-67 immunohistochemistry in patients with newly diagnosed and recurrent gliomas","volume":"53","author":"Yamamoto","year":"2012","journal-title":"J. Nucl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4714","DOI":"10.1200\/JCO.2006.10.5825","article-title":"Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: A pilot study","volume":"25","author":"Chen","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_26","first-page":"1432","article-title":"PET imaging with 18F-FLT and thymidine analogs: Promise and pitfalls","volume":"44","author":"Shields","year":"2003","journal-title":"J. Nucl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0163-7258(95)00015-9","article-title":"Mammalian deoxyribonuclease kinases","volume":"67","author":"Arner","year":"1995","journal-title":"Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"688","DOI":"10.3109\/10428194.2012.726722","article-title":"The role of clofarabine in acute myeloid leukemia","volume":"54","author":"Ghanem","year":"2013","journal-title":"Leuk. Lymphoma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"374","DOI":"10.2967\/jnumed.116.182394","article-title":"Human biodistribution and radiation dosimetry of 18F-clofarabine, a PET probe targeting the deoxyribonucleoside salvage pathway","volume":"58","author":"Barrio","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5551","DOI":"10.1073\/pnas.0913900107","article-title":"Requirement for deoxycytidine kinase in T and B lymphocyte development","volume":"107","author":"Toy","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10220","DOI":"10.1073\/pnas.1706689114","article-title":"Detection of immune responses after immunotherapy in glioblastoma using PET and MRI","volume":"114","author":"Antonios","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Treglia, G., Muoio, B., Trevisi, G., Mattoli, M.V., Albano, D., Bertagna, F., and Giovanella, L. (2019). Diagnostic Performance and Prognostic Value of PET\/CT with Different Tracers for Brain Tumors: A Systematic Review of Published Meta-Analyses. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194669"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1001\/jama.2013.280319","article-title":"Glioblastoma and other malignant gliomas: A clinical review","volume":"310","author":"Omuro","year":"2013","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1259\/0007-1285-26-312-638","article-title":"The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy","volume":"26","author":"Gray","year":"1953","journal-title":"Br. J. Radiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrclinonc.2012.171","article-title":"Imaging hypoxia to improve radiotherapy outcome","volume":"9","author":"Horsman","year":"2012","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"292","DOI":"10.2307\/3576986","article-title":"Characterization of radiolabeled fluoromisonidazole as a probe for hypoxic cells","volume":"111","author":"Rasey","year":"1987","journal-title":"Radiat. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/0360-3016(89)90146-6","article-title":"Radiolabeled fluoromisonidazole as an imaging agent for tumor hypoxia","volume":"17","author":"Rasey","year":"1989","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_38","first-page":"2133","article-title":"Hypoxia in human gliomas: Demonstration by PET with fluorine-18-fluoromisonidazole","volume":"33","author":"Valk","year":"1992","journal-title":"J. Nucl Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-08646-y","article-title":"FMISO-PET-derived brain oxygen tension maps: Application to glioblastoma and less aggressive gliomas","volume":"7","author":"Chakhoyan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1053\/j.semnuclmed.2014.10.001","article-title":"Hypoxia imaging in gliomas with 18F-fluoromisonidazole PET: Toward clinical translation","volume":"45","author":"Bell","year":"2015","journal-title":"Semin. Nucl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1007\/s00259-010-1517-y","article-title":"Biodistribution and dosimetry of 18F-EF5 in cancer patients with preliminary comparison of 18F-EF5 uptake versus EF5 binding in human glioblastoma","volume":"37","author":"Koch","year":"2010","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.2967\/jnumed.108.053785","article-title":"18F-EF5: A new PET tracer for imaging hypoxia in head and neck cancer","volume":"49","author":"Komar","year":"2008","journal-title":"J. Nucl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00259-002-1037-5","article-title":"Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5","volume":"30","author":"Ziemer","year":"2003","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0969-8043(00)00102-0","article-title":"[18F]-EF5, a marker for PET detection of hypoxia: Synthesis of precursor and a new fluorination procedure","volume":"54","author":"Dolbier","year":"2001","journal-title":"Appl. Radiat. Isot."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00259-002-1016-x","article-title":"Quantifying tumour hypoxia with fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) and PET using the tumour to plasma ratio","volume":"30","author":"Lehtioe","year":"2003","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_46","first-page":"1397","article-title":"Pharmacokinetics of [18F]FETNIM: A potential hypoxia marker for PET","volume":"42","author":"Gronroos","year":"2001","journal-title":"J. Nucl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1148\/radiology.194.3.7862981","article-title":"Development of F-18-labeled fluoroerythronitroimidazole as a PET agent for imaging tumor hypoxia","volume":"194","author":"Yang","year":"1995","journal-title":"Radiology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40658-016-0167-y","article-title":"Pharmacokinetic modeling of a novel hypoxia PET tracer [(18)F]HX4 in patients with non-small cell lung cancer","volume":"3","author":"Verwer","year":"2016","journal-title":"EJNMMI Phys."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"14620","DOI":"10.1073\/pnas.1102526108","article-title":"Preclinical evaluation and validation of [18F]HX4, a promising hypoxia marker for PET imaging","volume":"108","author":"Dubois","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s00259-010-1437-x","article-title":"PET imaging of hypoxia using [18F]HX4: A phase I trial","volume":"37","author":"Janssen","year":"2010","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1097\/MNM.0b013e3283407950","article-title":"Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and human determined by using whole-body PET\/CT","volume":"31","author":"Doss","year":"2010","journal-title":"Nucl. Med. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.3109\/0284186X.2015.1067721","article-title":"Comparison of [18F]-FMISO, [18F]-FAZA and [18F]-HX4 for PET imaging of hypoxia - a simulation study","volume":"54","author":"Wack","year":"2015","journal-title":"Acta Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ijrobp.2014.09.045","article-title":"A Comparative Study of the Hypoxia PET Tracers [18F]HX4, [18F]FAZA, and [18F]FMISO in a Preclinical Tumor Model","volume":"91","author":"Peeters","year":"2015","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Watanabe, S., Shiga, T., Hirata, K., Magota, K., Okamoto, S., Toyonaga, T., Higashikawa, K., Yasui, H., Kobayashi, J., and Nishijima, K.-I. (2019). Biodistribution and radiation dosimetry of the novel hypoxia PET probe [18F]DiFA and comparison with [18F]FMISO. EJNMMI Res.","DOI":"10.1186\/s13550-019-0525-6"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"106S","DOI":"10.2967\/jnumed.108.057281","article-title":"Radiopharmaceuticals in preclinical and clinical development for monitoring of therapy with PET","volume":"50","author":"Dunphy","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Floberg, J.M., Wang, L., Bandara, N., Rashmi, R., Mpoy, C., Garbow, J.R., Rogers, B.E., Patti, G.J., and Schwarz, J.K. (2019). Altering cellular reducing potential changes 64Cu-ATSM signal with or without hypoxia. J. Nucl. Med.","DOI":"10.2967\/jnumed.119.230805"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s12149-018-1241-4","article-title":"Prognostic implications of (62)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) PET\/CT in patients with glioma","volume":"32","author":"Toriihara","year":"2018","journal-title":"Ann. Nucl Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6429","DOI":"10.1021\/acs.inorgchem.7b00500","article-title":"Hypoxia-Responsive 19F MRI Probes with Improved Redox Properties and Biocompatibility","volume":"56","author":"Xie","year":"2017","journal-title":"Inorg. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1021\/jacs.5b13215","article-title":"Exploiting Copper Redox for 19F Magnetic Resonance-Based Detection of Cellular Hypoxia","volume":"138","author":"Xie","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s40336-017-0231-1","article-title":"Molecular mechanisms of hypoxia in cancer","volume":"5","author":"Challapalli","year":"2017","journal-title":"Clin. Transl. Imaging"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1002\/1097-0142(19850901)56:5<1106::AID-CNCR2820560525>3.0.CO;2-2","article-title":"Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications","volume":"56","author":"Burger","year":"1985","journal-title":"Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6864","DOI":"10.1038\/sj.onc.1204907","article-title":"Inhibition of human brain tumor cell growth by the anti-inflammatory drug, flurbiprofen","volume":"20","author":"King","year":"2001","journal-title":"Oncogene"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s40336-016-0168-9","article-title":"TSPO expression in brain tumours: Is TSPO a target for brain tumour imaging?","volume":"4","author":"Roncaroli","year":"2016","journal-title":"Clin. Transl. Imaging"},{"key":"ref_64","first-page":"1608","article-title":"PET study of carbon-11-PK 11195 binding to peripheral type benzodiazepine sites in glioblastoma: A case report","volume":"32","author":"Pappata","year":"1991","journal-title":"J. Nucl. Med."},{"key":"ref_65","first-page":"2691","article-title":"Expression of peripheral-type benzodiazepine receptor and diazepam binding inhibitor in human astrocytomas: Relationship to cell proliferation","volume":"55","author":"Miettinen","year":"1995","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11060-006-9199-9","article-title":"Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival","volume":"81","author":"Vlodavsky","year":"2007","journal-title":"J. Neuro-Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"512","DOI":"10.2967\/jnumed.114.151621","article-title":"The 18-kDa mitochondrial translocator protein in human gliomas: An 11C-(R) PK11195 PET imaging and neuropathology study","volume":"56","author":"Su","year":"2015","journal-title":"J. Nucl. Med."},{"key":"ref_68","first-page":"408","article-title":"Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines","volume":"55","author":"Vilner","year":"1995","journal-title":"Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1016\/j.ejca.2009.07.011","article-title":"Screening of anti-glioma effects induced by sigma-1 receptor ligands: Potential new use for old anti-psychiatric medicines","volume":"45","author":"Megalizzi","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neulet.2018.07.033","article-title":"Imaging sigma receptors in the brain: New opportunities for diagnosis of Alzheimer\u2019s disease and therapeutic development","volume":"691","author":"Jia","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.nucmedbio.2012.06.004","article-title":"Application of [11C]SA4503 to selection of novel \u03c31 selective agonists","volume":"39","author":"Toyohara","year":"2012","journal-title":"Nucl. Med. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0014-2999(96)00201-4","article-title":"Binding properties of SA4503, a novel and selective \u03c31 receptor agonist","volume":"306","author":"Matsuno","year":"1996","journal-title":"Eur. J. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/(SICI)1099-1344(199609)38:9<785::AID-JLCR901>3.0.CO;2-B","article-title":"Synthesis of [18F]-1-(3-Fluoropropyl)-4-(4-cyanophenoxymethyl)-piperidine: A potential sigma-1 receptor radioligand for PET","volume":"38","author":"Waterhouse","year":"1996","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/syn.20369","article-title":"In vitro and in vivo binding of neuroactive steroids to the sigma-1 receptor as measured with the positron emission tomography radioligand [18F]FPS","volume":"61","author":"Waterhouse","year":"2007","journal-title":"SYNAPSE"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8272","DOI":"10.1021\/jm300371c","article-title":"New Positron Emission Tomography (PET) Radioligand for Imaging \u03c3-1 Receptors in Living Subjects","volume":"55","author":"James","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kranz, M., Bergmann, R., Kniess, T., Belter, B., Neuber, C., Cai, Z., Deng, G., Fischer, S., Zhou, J., and Huang, Y. (2018). Bridging from brain to tumor imaging: (S)-(-)- and (R)-(+)-[18F]fluspidine for investigation of sigma-1 receptors in tumor-bearing mice. Molecules, 23.","DOI":"10.3390\/molecules23030702"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kranz, M., Sattler, B., W\u00fcst, N., Deuther-Conrad, W., Patt, M., Meyer, P., Fischer, S., Donat, C., W\u00fcnsch, B., and Hesse, S. (2016). Evaluation of the enantiomer specific biokinetics and radiation doses of [18F] fluspidine\u2014A new tracer in clinical translation for imaging of \u03c31 receptors. Molecules, 21.","DOI":"10.3390\/molecules21091164"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1054\/bjoc.1999.1067","article-title":"Sigma-2 receptors as a biomarker of proliferation in solid tumours","volume":"82","author":"Wheeler","year":"2000","journal-title":"Br. J. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/164_2016_96","article-title":"Molecular probes for imaging the sigma-2 receptor: In vitro and in vivo imaging studies","volume":"244","author":"Zeng","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7137","DOI":"10.1021\/jm301545c","article-title":"The \u03c32 Receptor: A Novel Protein for the Imaging and Treatment of Cancer","volume":"56","author":"Mach","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_81","first-page":"3022","article-title":"Synthesis and pharmacological characterization of 4-[125I]-N-(N-benzylpiperidin-4-yl)-4-iodobenzamide: A high affinity or receptor ligand for potential imaging of breast cancer","volume":"55","author":"John","year":"1995","journal-title":"Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0969-8051(98)00104-8","article-title":"Synthesis, in vitro pharmacologic characterization, and preclinical evaluation of N-[2-(1\u2019-piperidinyl)ethyl]-3-[125I]iodo-4-methoxybenzamide (P[125I]MBA) for imaging breast cancer","volume":"26","author":"John","year":"1999","journal-title":"Nucl. Med. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1476-4598-6-48","article-title":"Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: Applications in diagnostic imaging and therapy","volume":"6","author":"Kashiwagi","year":"2007","journal-title":"Mol. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"350","DOI":"10.2967\/jnumed.112.111948","article-title":"Assessment of cellular proliferation in tumors by PET using 18F-ISO-1","volume":"54","author":"Dehdashti","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Shoghi, K.I., Xu, J., Su, Y., He, J., Rowland, D., Yan, Y., Garbow, J.R., Tu, Z., Jones, L.A., and Higashikubo, R. (2013). Quantitative receptor-based imaging of tumor proliferation with the sigma-2 ligand [18F]ISO-1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074188"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1158\/1078-0432.CCR-18-2769","article-title":"Cell-Proliferation Imaging for Monitoring Response to CDK4\/6 Inhibition Combined with Endocrine-Therapy in Breast Cancer: Comparison of [(18)F]FLT and [(18)F]ISO-1 PET\/CT","volume":"25","author":"Elmi","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/2191-219X-3-80","article-title":"Synthesis and biological characterization of 18F-SIG343 and 18F-SIG353, novel and high selectivity \u03c32 radiotracers, for tumor imaging properties","volume":"3","author":"Nguyen","year":"2013","journal-title":"EJNMMI Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.ejmech.2013.09.018","article-title":"Development of 3,4-dihydroisoquinolin-1(2H)-one derivatives for the Positron Emission Tomography (PET) imaging of \u03c32 receptors","volume":"69","author":"Abate","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.nucmedbio.2014.12.018","article-title":"Synthesis and pharmacological evaluation of 11C-labeled piperazine derivative as a PET probe for sigma-2 receptor imaging","volume":"42","author":"Selivanova","year":"2015","journal-title":"Nucl. Med. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1016\/j.bmc.2017.05.019","article-title":"18F-Labeled indole-based analogs as highly selective radioligands for imaging sigma-2 receptors in the brain","volume":"25","author":"Wang","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1021\/acs.bioconjchem.6b00348","article-title":"PD-L1 Detection in Tumors Using [(64)Cu]Atezolizumab with PET","volume":"27","author":"Lesniak","year":"2016","journal-title":"Bioconjug Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.bbrc.2016.12.156","article-title":"Rapid PD-L1 detection in tumors with PET using a highly specific peptide","volume":"483","author":"Chatterjee","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2967\/jnumed.116.177659","article-title":"Practical Immuno-PET Radiotracer Design Considerations for Human Immune Checkpoint Imaging","volume":"58","author":"Mayer","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.2967\/jnumed.117.191718","article-title":"In Vivo Imaging of the Programmed Death Ligand 1 by (18)F PET","volume":"58","author":"Gonzalez","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_95","unstructured":"Miller, M.M., Mapelli, C., Allen, M.P., Bowsher, M.S., Boy, K.M., Gillis, E.P., Langley, D.R., Mull, E., Poirier, M.A., and Sanghvi, N. (2016). Macrocyclic inhibitors of the PD-1\/PD-L1 and CD80 (B7-1)\/PD-L1 protein\/protein interactions. (US9308236B2)."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"30323","DOI":"10.18632\/oncotarget.8730","article-title":"Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1)","volume":"7","author":"Zak","year":"2016","journal-title":"Oncotarget"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4840","DOI":"10.1002\/anie.201710407","article-title":"Immune Checkpoint PD-1\/PD-L1: Is There Life Beyond Antibodies?","volume":"57","author":"Konstantinidou","year":"2018","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.ejmech.2018.10.044","article-title":"Peptide-based and small synthetic molecule inhibitors on PD-1\/PD-L1 pathway: A new choice for immunotherapy?","volume":"161","author":"Chen","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Lee, H.T., Lee, S.H., and Heo, Y.-S. (2019). Molecular interactions of antibody drugs targeting PD-1, PD-L1, and CTLA-4 in immuno-oncology. Molecules, 24.","DOI":"10.3390\/molecules24061190"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1101\/gad.1331805","article-title":"Poly(ADP-ribosyl)ation by PARP-1: \u2018PAR-laying\u2019 NAD+ into a nuclear signal","volume":"19","author":"Kim","year":"2005","journal-title":"Genes Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nrm.2017.53","article-title":"The multifaceted roles of PARP1 in DNA repair and chromatin remodelling","volume":"18","author":"Nussenzweig","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ejmech.2019.01.024","article-title":"Medicinal chemistry approaches of poly ADP-Ribose polymerase 1 (PARP1) inhibitors as anticancer agents\u2014A recent update","volume":"165","author":"Jain","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1593\/neo.12414","article-title":"Imaging therapeutic PARP inhibition in vivo through bioorthogonally developed companion imaging agents","volume":"14","author":"Reiner","year":"2012","journal-title":"Neoplasia"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.neo.2014.05.005","article-title":"PARPi-FL-a fluorescent PARP1 inhibitor for glioblastoma imaging","volume":"16","author":"Irwin","year":"2014","journal-title":"Neoplasia"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s11307-015-0904-y","article-title":"Non-invasive PET imaging of PARP1 expression in glioblastoma models","volume":"18","author":"Carney","year":"2016","journal-title":"Mol. Imaging Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1158\/0008-5472.CAN-16-2850","article-title":"Biomarker-Based PET Imaging of Diffuse Intrinsic Pontine Glioma in Mouse Models","volume":"77","author":"Kossatz","year":"2017","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"504","DOI":"10.2967\/jnumed.118.213223","article-title":"PET Imaging of PARP Expression Using 18F-Olaparib","volume":"60","author":"Wilson","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.bmc.2014.01.019","article-title":"Synthesis, [18F] radiolabeling, and evaluation of poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors for in vivo imaging of PARP-1 using positron emission tomography","volume":"22","author":"Zhou","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1148\/radiol.2016161929","article-title":"PET of Poly (ADP-Ribose) Polymerase Activity in Cancer: Preclinical Assessment and First In-Human Studies","volume":"282","author":"Michel","year":"2016","journal-title":"Radiology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1056\/NEJMoa0808710","article-title":"IDH1 and IDH2 Mutations in Gliomas","volume":"360","author":"Yan","year":"2009","journal-title":"New Engl. J. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1200\/JCO.2009.21.9832","article-title":"Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas","volume":"27","author":"Sanson","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ccr.2013.03.005","article-title":"R-2-hydroxyglutarate as the key effector of IDH mutations promoting oncogenesis","volume":"23","author":"Ye","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Kaminska, B., Czapski, B., Guzik, R., Krol, S.K., and Gielniewski, B. (2019). Consequences of IDH1\/2 mutations in gliomas and an assessment of inhibitors targeting mutated IDH proteins. Molecules, 24.","DOI":"10.3390\/molecules24050968"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1021\/acsmedchemlett.7b00421","article-title":"Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers","volume":"9","author":"Lemieux","year":"2018","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1021\/acsmedchemlett.7b00342","article-title":"Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor","volume":"8","author":"Cho","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1182\/blood.V128.22.1073.1073","article-title":"A Phase I Study of IDH305 in Patients with Advanced Malignancies Including Relapsed\/Refractory AML and MDS That Harbor IDH1R132 Mutations","volume":"128","author":"DiNardo","year":"2016","journal-title":"Blood"},{"key":"ref_117","unstructured":"Chi, A.S. (2019, September 30). Trial of IDH305 in IDH1 Mutant Grade II or III Glioma, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02977689."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s12149-018-01328-3","article-title":"18F-DOPA uptake does not correlate with IDH mutation status and 1p\/19q co-deletion in glioma","volume":"33","author":"Cicone","year":"2019","journal-title":"Ann. Nucl. Med."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Blanc-Durand, P., Van Der Gucht, A., Verger, A., Langen, K.-J., Dunet, V., Bloch, J., Brouland, J.-P., Nicod-Lalonde, M., Schaefer, N., and Prior, J.O. (2018). Voxel-based 18F-FET PET segmentation and automatic clustering of tumor voxels: A significant association with IDH1 mutation status and survival in patients with gliomas. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199379"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1007\/s00259-018-3969-4","article-title":"Biological tumour volumes of gliomas in early and standard 20-40 min 18F-FET PET images differ according to IDH mutation status","volume":"45","author":"Unterrrainer","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00259-017-3846-6","article-title":"Static and dynamic 18F-FET PET for the characterization of gliomas defined by IDH and 1p\/19q status","volume":"45","author":"Verger","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.bmcl.2018.01.015","article-title":"Synthesis and evaluation of radiolabeled AGI-5198 analogues as candidate radiotracers for imaging mutant IDH1 expression in tumors","volume":"28","author":"Chitneni","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1021\/acsmedchemlett.7b00478","article-title":"Synthesis and Evaluation of a 18F-Labeled Triazinediamine Analogue for Imaging Mutant IDH1 Expression in Gliomas by PET","volume":"9","author":"Chitneni","year":"2018","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e3775","DOI":"10.1002\/nbm.3775","article-title":"Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study","volume":"30","author":"Preibisch","year":"2017","journal-title":"NMR Biomed."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"5525","DOI":"10.1088\/0031-9155\/54\/18\/012","article-title":"The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma","volume":"54","author":"Thiele","year":"2009","journal-title":"Phys. Med. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2967\/jnumed.115.158717","article-title":"18F-fluoromisonidazole quantification of hypoxia in human cancer patients using image-derived blood surrogate tissue reference regions","volume":"56","author":"Muzi","year":"2015","journal-title":"J. Nucl. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/3\/568\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:08:43Z","timestamp":1760364523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/3\/568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,28]]},"references-count":126,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["molecules25030568"],"URL":"https:\/\/doi.org\/10.3390\/molecules25030568","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,28]]}}}