Fatania Kavi, Frood Russell, Tyyger Marcus, McDermott Garry, Fernandez Sharon, Shaw Gary C, Boissinot Marjorie, Salvatore Daniela, Ottobrini Luisa, Teh Irvin, Wright John, Bailey Marc A, Koch-Paszkowski Joanna, Schneider Jurgen E, Buckley David L, Murray Louise, Scarsbrook Andrew, Short Susan C, Currie Stuart
Department of Radiology, Leeds Teaching Hospitals Trust, Leeds General Infirmary, Leeds LS1 3EX, UK.
Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9TJ, UK.
Cancers (Basel). 2022 Jul 18;14(14):3485. doi: 10.3390/cancers14143485.
Anti-1-amino-3-fluorine-fluorocyclobutane-1-carboxylic acid (F-fluciclovine) positron emission tomography (PET) shows preferential glioma uptake but there is little data on how uptake correlates with post-contrast T1-weighted (Gd-T1) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) activity during adjuvant treatment. This pilot study aimed to compare F-fluciclovine PET, DCE-MRI and Gd-T1 in patients undergoing chemoradiotherapy for glioblastoma (GBM), and in a parallel pre-clinical GBM model, to investigate correlation between F-fluciclovine uptake, MRI findings, and tumour biology. F-fluciclovine-PET-computed tomography (PET-CT) and MRI including DCE-MRI were acquired before, during and after adjuvant chemoradiotherapy (60 Gy in 30 fractions with temozolomide) in GBM patients. MRI volumes were manually contoured; PET volumes were defined using semi-automatic thresholding. The similarity of the PET and DCE-MRI volumes outside the Gd-T1 volume boundary was measured using the Dice similarity coefficient (DSC). CT-2A tumour-bearing mice underwent MRI and F-fluciclovine PET-CT. Post-mortem mice brains underwent immunohistochemistry staining for ASCT2 (amino acid transporter), nestin (stemness) and Ki-67 (proliferation) to assess for biologically active tumour. 6 patients were recruited (GBM 1-6) and grouped according to overall survival (OS)-short survival (GBM-SS, median OS 249 days) and long survival (GBM-LS, median 903 days). For GBM-SS, PET tumour volumes were greater than DCE-MRI, in turn greater than Gd-T1. For GBM-LS, Gd-T1 and DCE-MRI were greater than PET. Tumour-specific F-fluciclovine uptake on pre-clinical PET-CT corresponded to immunostaining for Ki-67, nestin and ASCT2. Results suggest volumes of F-fluciclovine-PET activity beyond that depicted by DCE-MRI and Gd-T1 are associated with poorer prognosis in patients undergoing chemoradiotherapy for GBM. The pre-clinical model confirmed F-fluciclovine uptake reflected biologically active tumour.
抗1-氨基-3-氟-氟环丁烷-1-羧酸（F-氟西洛维）正电子发射断层扫描（PET）显示胶质瘤有优先摄取，但关于摄取与辅助治疗期间的对比增强T1加权（Gd-T1）和动态对比增强磁共振成像（DCE-MRI）活性之间的相关性数据很少。这项初步研究旨在比较胶质母细胞瘤（GBM）放化疗患者以及平行的临床前GBM模型中的F-氟西洛维PET、DCE-MRI和Gd-T1，以研究F-氟西洛维摄取、MRI表现和肿瘤生物学之间的相关性。在GBM患者辅助放化疗（60 Gy分30次，联合替莫唑胺）之前、期间和之后进行F-氟西洛维PET计算机断层扫描（PET-CT）和包括DCE-MRI在内的MRI检查。MRI体积通过手动勾勒轮廓；PET体积使用半自动阈值定义。使用骰子相似系数（DSC）测量Gd-T1体积边界外的PET和DCE-MRI体积的相似性。对荷CT-2A肿瘤的小鼠进行MRI和F-氟西洛维PET-CT检查。对死后小鼠大脑进行ASCT2（氨基酸转运体）、巢蛋白（干性）和Ki-67（增殖）免疫组织化学染色，以评估生物活性肿瘤。招募了6名患者（GBM 1-6），并根据总生存期（OS）分为短生存期（GBM-SS，中位OS 249天）和长生存期（GBM-LS，中位903天）。对于GBM-SS，PET肿瘤体积大于DCE-MRI，DCE-MRI又大于Gd-T1。对于GBM-LS，Gd-T1和DCE-MRI大于PET。临床前PET-CT上肿瘤特异性F-氟西洛维摄取与Ki-67、巢蛋白和ASCT2免疫染色相对应。结果表明，F-氟西洛维PET活性超出DCE-MRI和Gd-T1所示范围的体积与GBM放化疗患者的预后较差相关。临床前模型证实F-氟西洛维摄取反映了生物活性肿瘤。
