Center for Molecular Imaging and Experimental Radiotherapy, Université catholique de Louvain, St-Luc University Hospital, Brussels, Belgium.
Radiother Oncol. 2010 Nov;97(2):183-8. doi: 10.1016/j.radonc.2010.02.020. Epub 2010 Mar 19.
Fluorodeoxyglucose (FDG) has been reported as a surrogate tracer to measure tumor hypoxia with positron emission tomography (PET). The hypothesis is that there is an increased uptake of FDG under hypoxic conditions secondary to enhanced glycolysis, compensating the hypoxia-induced loss of cellular energy production. Several studies have already addressed this issue, some with conflicting results. This study aimed to compare the tracers (14)C-EF3 and (18)F-FDG to detect hypoxia in mouse tumor models.
C3H, tumor-bearing mice (FSAII and SCCVII tumors) were injected iv with (14)C-EF3, and 1h later with (18)F-FDG. Using a specifically designed immobilization device with fiducial markers, PET (Mosaic®, Philips) images were acquired 1h after the FDG injection. After imaging, the device containing mouse was frozen, transversally sliced and imaged with autoradiography (AR) (FLA-5100, Fujifilm) to obtain high resolution images of the (18)F-FDG distribution within the tumor area. After a 48-h delay allowing for (18)F decay a second AR was performed to image (14)C-EF3 distribution. AR images were aligned to reconstruct the full 3D tumor volume, and were compared with the PET images. Image segmentation with threshold-based methods was applied on both AR and PET images to derive various tracer activity volumes. The matching index DSI (dice similarity index) was then computed. The comparison was performed under normoxic (ambient air, FSAII: n=4, SCCVII, n=5) and under hypoxic conditions (10% O(2) breathing, SCCVII: n=4).
On AR, under both ambient air and hypoxic conditions, there was a decreasing similarity between (14)C-EF3 and FDG with higher activity sub-volumes. Under normoxic conditions, when comparing the 10% of tumor voxels with the highest (18)F-FDG or (14)C-EF3 activity, a DSI of 0.24 and 0.20 was found for FSAII and SCCVII, respectively. Under hypoxic conditions, a DSI of 0.36 was observed for SCCVII tumors. When comparing the (14)C-EF3 distribution in AR with the corresponding (18)F-FDG-PET images, the DSI reached values of 0.26, 0.22 and 0.21 for FSAII and SCCVII under normoxia and SCCVII under hypoxia, respectively.
This study showed that FDG is not a good surrogate tracer for tumor hypoxia under either ambient or hypoxic conditions. Only specific hypoxia tracers should be used to measure tumor hypoxia.
氟代脱氧葡萄糖（FDG）已被报道为一种示踪剂，可通过正电子发射断层扫描（PET）测量肿瘤缺氧。其假设是，在缺氧条件下，由于糖酵解增强，FDG 的摄取增加，从而补偿了细胞能量产生的缺氧诱导损失。已有几项研究已经解决了这个问题，其中一些研究结果存在矛盾。本研究旨在比较示踪剂（14）C-EF3 和（18）F-FDG 在检测小鼠肿瘤模型中的缺氧情况。
C3H，荷瘤小鼠（FSAII 和 SCCVII 肿瘤）静脉注射（14）C-EF3，1 小时后注射（18）F-FDG。使用专门设计的带有基准标记的固定装置，在 FDG 注射后 1 小时采集 PET（Mosaic®，飞利浦）图像。成像后，将含有小鼠的装置冷冻，横向切片，并进行放射性自显影（AR）（FLA-5100，富士胶片）成像，以获得肿瘤区域内（18）F-FDG 分布的高分辨率图像。延迟 48 小时以允许（18）F 衰变后，进行第二次 AR 以成像（14）C-EF3 分布。AR 图像与 PET 图像对齐以重建完整的 3D 肿瘤体积，并进行比较。使用基于阈值的方法对 AR 和 PET 图像进行图像分割，以得出各种示踪剂活性体积。然后计算匹配指数 DSI（骰子相似性指数）。在常氧（环境空气，FSAII：n=4，SCCVII，n=5）和低氧条件（10% O2 呼吸，SCCVII：n=4）下进行比较。
在 AR 上，在环境空气和低氧条件下，（14）C-EF3 和 FDG 之间的相似性随着更高活性子体积的降低而降低。在常氧条件下，当比较具有最高（18）F-FDG 或（14）C-EF3 活性的 10%肿瘤体素时，FSAII 和 SCCVII 的 DSI 分别为 0.24 和 0.20。在低氧条件下，SCCVII 肿瘤的 DSI 为 0.36。当将 AR 中的（14）C-EF3 分布与相应的（18）F-FDG-PET 图像进行比较时，FSAII 和 SCCVII 在常氧条件下以及 SCCVII 在低氧条件下的 DSI 分别达到 0.26、0.22 和 0.21。
本研究表明，FDG 不是环境或低氧条件下肿瘤缺氧的良好示踪剂。仅应使用特定的缺氧示踪剂来测量肿瘤缺氧。
