Lapa Constantin, Lückerath Katharina, Kleinlein Irene, Monoranu Camelia Maria, Linsenmann Thomas, Kessler Almuth F, Rudelius Martina, Kropf Saskia, Buck Andreas K, Ernestus Ralf-Ingo, Wester Hans-Jürgen, Löhr Mario, Herrmann Ken
1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany; 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 3. Institute of Pathology, University of Würzburg, Würzburg, Germany.
Theranostics. 2016 Jan 25;6(3):428-34. doi: 10.7150/thno.13986. eCollection 2016.
Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand (68)Ga-Pentixafor. 15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent (68)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUVmax, SUVmean). Tumor-to-background ratios (TBR) were calculated for both PET probes. (68)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples. (68)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUVmean and SUVmax of 3.0±1.5 and 3.9±2.0 respectively. Respective values for (18)F-FET were 4.4±2.0 (SUVmean) and 5.3±2.3 (SUVmax). TBR for SUVmean and SUVmax were higher for (68)Ga-Pentixafor than for (18)F-FET (SUVmean 154.0±90.7 vs. 4.1±1.3; SUVmax 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high (68)Ga-Pentixafor uptake; regions of the same tumor without apparent (68)Ga-Pentixafor uptake showed no or low receptor expression. In this pilot study, (68)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, (68)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
据报道，趋化因子受体4（CXCR4）在胶质母细胞瘤（GBM）中过表达，并与较差的生存率相关。本研究使用放射性标记的趋化因子受体配体（68）Ga - Pentixafor，探讨了正电子发射断层扫描/计算机断层扫描（PET/CT）对CXCR4进行无创成像的可行性。15例临床怀疑为原发性或复发性胶质母细胞瘤的患者（13例原发性肿瘤，2例复发性肿瘤）在手术前行（68）Ga - Pentixafor - PET/CT以评估CXCR4表达。15例中有11例可获得O -（2 -（18）F - 氟乙基）- L - 酪氨酸（（18）F - FET）PET/CT图像，并进行了视觉和半定量比较（SUVmax，SUVmean）。计算了两种PET探针的肿瘤与背景比值（TBR）。（68）Ga - Pentixafor - PET/CT结果也与神经导航手术样本上的组织学CXCR4表达进行了比较。（68）Ga - Pentixafor - PET/CT在15例中有13例视觉上呈阳性，SUVmean和SUVmax分别为3.0±1.5和3.9±2.0。（18）F - FET的相应值为4.4±2.0（SUVmean）和5.3±2.3（SUVmax）。（68）Ga - Pentixafor的SUVmean和SUVmax的TBR高于（18）F - FET（SUVmean分别为154.0±90.7 vs. 4.1±1.3；SUVmax分别为70.3±44.0和3.8±1.2，p<0.01）。组织学分析证实，（68）Ga - Pentixafor摄取高的肿瘤区域有CXCR4表达；同一肿瘤中无明显（68）Ga - Pentixafor摄取的区域显示无或低受体表达。在这项初步研究中，在绝大多数胶质母细胞瘤病变中观察到了（68）Ga - Pentixafor滞留，并作为无创测定CXCR4表达的指标。鉴于CXCR4/SDF - 1轴在肿瘤生物学中的至关重要性，（68）Ga - Pentixafor - PET/CT可能是一种用于敏感、无创体内定量CXCR4以及选择可能从CXCR4导向治疗中获益的患者的有用工具。
