Nedergaard Mette Kjoelhede, Michaelsen Signe Regner, Urup Thomas, Broholm Helle, El Ali Henrik, Poulsen Hans Skovgaard, Stockhausen Marie-Thérése, Kjaer Andreas, Lassen Ulrik
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Department of Radiation Biology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark.
PLoS One. 2015 Feb 13;10(2):e0115315. doi: 10.1371/journal.pone.0115315. eCollection 2015.
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 SUV max 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.
关于抗胎盘生长因子（抗PlGF）与抗血管内皮生长因子（抗VEGF）联合使用的抗癌效果，存在相互矛盾的数据。尽管如此，这种联合治疗尚未在颅内胶质母细胞瘤（GBM）异种移植模型中进行评估。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）的正电子发射断层扫描（PET）和磁共振成像（MRI）可提供关于胶质瘤生长的互补但不同的信息；然而，18F-FET微型PET与微型MRI联合使用的价值尚未在临床前进行研究。在此，我们研究了使用18F-FET微型PET和微型MRI评估GBM异种移植模型中抗VEGF和抗PlGF治疗反应的情况。
将颅内GBM小鼠分别用抗VEGF、抗PlGF +抗VEGF或生理盐水进行治疗。使用生物发光成像（BLI）、18F-FET微型PET和T2加权（T2w）-MRI来跟踪肿瘤的发展。主要终点是生存期，随后对肿瘤进行Ki67增殖指数和微血管密度（MVD）分析。此外，在一部分异种移植肿瘤和13例GBM患者肿瘤中检测了PlGF和VEGFR-1的表达。
抗VEGF单药治疗可延长生存期，并降低18F-FET摄取、BLI和MVD，而未观察到抗PlGF的附加效应。与对照组相比，抗VEGF组在治疗1周后（114±6%，n = 11 vs. 143±8%，n = 13；p = 0.02）和2周后（116±12%，n = 8 vs. 190±24%，n = 5；p = 0.02），18F-FET SUV max肿瘤与脑（T/B）比值显著降低。相比之下，T2w-MRI体积不受抗VEGF影响。异种移植肿瘤中PlGF和VEGFR-1的基因表达显著低于患者肿瘤。
18F-FET PET可用于评估抗血管生成反应，且优于T2w-MRI；然而，未观察到抗PlGF和抗VEGF的附加抗癌效应。因此，本研究支持在未来研究中使用18F-FET PET进行反应评估。
Zotero 插件
