title: (68)Ga-PRGD2 PET/CT in the evaluation of Glioma: a prospective study.
abstract: Integrin αvβ3 is overexpressed in both neovasculature and glioma cells. We aimed to evaluate (68)gallium-BNOTA-PRGD2 ((68)Ga-PRGD2) as a new reagent for noninvasive integrin αvβ3 imaging in glioma patients. With informed consent, 12 patients with suspicious brain glioma, as diagnosed by enhanced magnetic resonance imaging (MRI) scanning, were enrolled to undergo (68)Ga-PRGD2 PET/CT and (18)F-FDG PET/CT scans before surgery. The preoperative images were compared and correlated with the pathologically determined WHO grade. Next, the expression of integrin αvβ3, CD34, and Ki-67 were determined by immunohistochemical staining of the resected brain tumor tissue. Our findings demonstrated that (68)Ga-PRGD2 specifically accumulated in the brain tumors that were rich of integrin αvβ3 and other neovasculature markers, but not in the brain parenchyma other than the choroid plexus. Therefore, (68)Ga-PRGD2 PET/CT was able to evaluate the glioma demarcation more specifically than (18)F-FDG PET/CT. The maximum standardized uptake values (SUVmax) of (68)Ga-PRGD2, rather than those of (18)F-FDG, were significantly correlated with the glioma grading. The maximum tumor-to-brain ratios (TBRmax) of both tracers were significantly correlated with glioma grading, whereas (68)Ga-PRGD2 seemed to be more superior to (18)F-FDG in differentiating high-grade glioma (HGG) from low-grade glioma (LGG). Moreover, (68)Ga-PRGD2 PET/CT showed different accumulation patterns for HGG of WHO grades III and IV. This is the first noninvasive integrin imaging study, to the best of our knowledge, conducted in preoperative patients with different grades of glioma, and it preliminarily indicated the effectiveness of this novel method for evaluating glioma grading and demarcation.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University ; China National Clinical Research Center for Neurological Diseases (NCRC-ND); Beijing Key Laboratory of Brian Tumor, Beijing, China.
authors.forename: Deling
authors.initials: D
authors.lastname: Li
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zhao
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Ji
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Gao
authors.forename: Jisheng
authors.initials: J
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Kang
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D002831:Choroid Plexus / Q000378:metabolism; D056831:Coordination Complexes; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D005710:Gallium Radioisotopes; D005910:Glioma / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: C000599881:68gallium-BNOTA-PRGD2; D018952:Antigens, CD34; D056831:Coordination Complexes; D005710:Gallium Radioisotopes; D039302:Integrin alphaVbeta3; D019394:Ki-67 Antigen; D010455:Peptides; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: 68Ga; PET/CT; glioma; integrin αvβ3
references.citation: J Nucl Med. 2007 Sep;48(9):1468-81
references.pmid: 17704239
references.citation: J Nucl Med. 2013 Feb;54(2):229-35
references.pmid: 23232275
references.citation: Mol Imaging Biol. 2010 Oct;12(5):530-8
references.pmid: 19949981
references.citation: AJNR Am J Neuroradiol. 2013 Jan;34(1):92-9
references.pmid: 22700754
references.citation: Neuroradiology. 2011 Dec;53(12):1017-24
references.pmid: 21739222
references.citation: J Nucl Med. 2012 May;53(5):787-95
references.pmid: 22499613
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3475-80
references.pmid: 22345562
references.citation: Science. 2014 Jan 3;343(6166):72-6
references.pmid: 24310612
references.citation: J Neurooncol. 2012 Jan;106(1):147-53
references.pmid: 21739168
references.citation: Neuro Oncol. 2011 Aug;13(8):857-65
references.pmid: 21788343
references.citation: Mol Imaging. 2013 Jan-Feb;12(1):39-48
references.pmid: 23348790
references.citation: Bioconjug Chem. 2011 Dec 21;22(12):2415-22
references.pmid: 22026940
references.citation: Brain Pathol. 2008 Jul;18(3):378-86
references.pmid: 18394009
references.citation: Acta Neuropathol. 2012 Dec;124(6):763-75
references.pmid: 23143192
references.citation: Anticancer Res. 2012 Oct;32(10):4213-23
references.pmid: 23060541
references.citation: J Nucl Med. 2005 Oct;46(10):1707-18
references.pmid: 16204722
references.citation: J Neuropathol Exp Neurol. 2013 Mar;72(3):194-210
references.pmid: 23399898
references.citation: Acta Neuropathol. 2007 Aug;114(2):97-109
references.pmid: 17618441
references.citation: J Biol Chem. 2013 Jan 4;288(1):343-54
references.pmid: 23161541
references.citation: AJNR Am J Neuroradiol. 2013 May;34(5):944-50, S1-11
references.pmid: 23124638
references.citation: Radiology. 1995 Apr;195(1):47-52
references.pmid: 7892494
references.citation: Cancer. 2012 Nov 15;118(22):5601-7
references.pmid: 22517399
references.citation: Mol Pharm. 2013 Sep 3;10(9):3304-14
references.pmid: 23875883
references.citation: J Biol Chem. 2001 Dec 14;276(50):47171-7
references.pmid: 11572856
references.citation: Radiology. 2009 Nov;253(2):462-9
references.pmid: 19789239
references.citation: Nucl Med Biol. 2012 Oct;39(7):977-81
references.pmid: 22483845
references.citation: J Mol Biol. 2003 Mar 7;326(5):1475-88
references.pmid: 12595259
references.citation: Neuro Oncol. 2013 Oct;15(10):1438-44
references.pmid: 24014381
references.citation: Nucl Med Biol. 2013 May;40(4):481-7
references.pmid: 23618768
references.citation: J Biomed Biotechnol. 2012;2012:205818
references.pmid: 22577290
references.citation: Neuro Oncol. 2009 Dec;11(6):861-70
references.pmid: 19401596
references.citation: Neuro Oncol. 2011 Aug;13(8):806-19
references.pmid: 21757446