18F-FET microPET and microMRI for anti-VEGF and anti-PlGF response assessment in an orthotopic murine model of human glioblastoma.
18F-FET microPET and microMRI for anti-VEGF and anti-PlGF response assessment in an orthotopic murine model of human glioblastoma.
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DOI：
10.1371/journal.pone.0115315
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lassen U
中科院分区：
文献类型：
--
作者：
Nedergaard MK;Michaelsen SR;Urup T;Broholm H;El Ali H;Poulsen HS;Stockhausen MT;Kjaer A;Lassen U
关于抗胎盘生长因子(抗PlGF)和抗血管内皮生长因子(VEGF)联合使用的抗癌作用，存在相互矛盾的数据。尽管如此，这种治疗组合还没有在颅内胶质母细胞瘤(GBM)异种移植中得到评估。在临床研究中，使用放射性标记氨基酸O-(2-18F-氟乙基)-L-酪氨酸(18F-FET)的位置发射断层扫描(PET)和磁共振成像(MRI)增加了关于胶质瘤生长的补充但不同的信息；然而，18F-FET microPET结合MicroMRI的价值尚未得到临床前的研究。在这里，我们研究了18F-FET、microPET和MicroMRI在评估抗血管内皮生长因子和抗PlGF治疗反应方面的作用。用抗血管内皮生长因子抗体、抗PlGF+抗血管内皮生长因子抗体或生理盐水治疗颅内GBM小鼠。使用生物发光成像(BLI)、18F-FET microPET和T2加权(T2w)-MRI跟踪肿瘤的发展。主要终点是生存，随后分析肿瘤的Ki67增殖指数和微血管密度(MVD)。此外，在部分异种移植瘤和13例GBM患者肿瘤中检测了PlGF和VEGFR-1的表达。抗血管内皮生长因子单药治疗可提高存活率，降低18F-FET摄取、BLI和MVD，而抗PlGF未见相加作用。治疗后1周(114±6%，n=11比143±8%，n=13；P=0.02)和治疗2周(116±12%，n=8比190±24%，n=5；P=0.02)，抗血管内皮生长因子治疗组18F-FET SUVmax肿瘤/脑(T/B)比值明显低于对照组。反之，抗血管内皮生长因子抗体对T2w-MRI体积无明显影响。移植瘤中PlGF和VEGFR-1的基因表达显著低于患者肿瘤。18F-FET PET用于抗血管生成反应的评价是可行的，优于T2w-MRI，但未观察到抗PlGF和抗VEGF的相加抗癌作用。因此，这项研究支持在未来的研究中使用18F-FET PET进行反应评估。
Conflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of 18F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of 18F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts. Mice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), 18F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours. Anti-VEGF monotherapy increased survival and decreased 18F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. 18F-FET SUVmax tumour-to-brain (T/B) ratio was significantly lower after one week (114±6%, n = 11 vs. 143±8%, n = 13; p = 0.02) and two weeks of treatment (116±12%, n = 8 vs. 190±24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours. 18F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of 18F-FET PET for response evaluation in future studies.
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影响因子：
5.6
作者：
Pope, Whitney B.;Young, Jonathan R.;Ellingson, Benjamin M.
通讯作者：
Ellingson, Benjamin M.
影响因子：
64.5
作者：
Fischer, Christian;Jonckx, Bart;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
DOI：
10.1073/pnas.1209310110
发表时间：
2013-01-08
影响因子：
11.1
作者：
Hedlund, Eva-Maria Eleonora;Yang, Xiaojuan;Cao, Yihai
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Cao, Yihai
DOI：
10.1007/s00259-012-2251-4
发表时间：
2013-01-01
影响因子：
9.1
作者：
Galldiks, Norbert;Rapp, Marion;Langen, Karl-Josef
通讯作者：
Langen, Karl-Josef
DOI：
10.1007/s00259-005-1819-7
发表时间：
2005-09-01
影响因子：
9.1
作者：
Pöpperl, G;Goldbrunner, R;Tatsch, K
通讯作者：
Tatsch, K