Dubois Ludwig, Landuyt Willy, Cloetens Lieselotte, Bol Anne, Bormans Guy, Haustermans Karin, Labar Daniel, Nuyts Johan, Grégoire Vincent, Mortelmans Luc
Department of Nuclear Medicine, University Hospital Gasthuisberg and KU Leuven, 3000, Leuven, Belgium.
Eur J Nucl Med Mol Imaging. 2009 Feb;36(2):209-18. doi: 10.1007/s00259-008-0907-x. Epub 2008 Aug 9.
The aim of this investigation was to quantitatively compare the novel positron emission tomography (PET) hypoxia marker 2-(2-nitroimidazol-1-yl)-N-(3[(18)F],3,3-trifluoropropyl)acetamide ([(18)F]EF3) with the reference hypoxia tracer [(18)F]fluoromisonidazole ([(18)F]FMISO).
[(18)F]EF3 or [(18)F]FMISO was injected every 2 days into two separate groups of rats bearing syngeneic rhabdomyosarcoma tumours. In vivo PET analysis was done by drawing regions of interest on the images of selected tissues. The resulting activity data were quantified by the percentage of injected radioactivity per gram tissue (%ID/g) and tumour to blood (T/B) ratio. The spatial distribution of radioactivity was defined by autoradiography on frozen tumour sections.
The blood clearance of [(18)F]EF3 was faster than that of [(18)F]FMISO. The clearance of both tracers was slower in tumour tissue compared with other tissues. This results in increasing T/B ratios as a function of time post tracer injection (p.i.). The maximal [(18)F]EF3 tumour uptake, compared to the maximum [(18)F]FMISO uptake, was significantly lower at 2 h p.i. but reached similar levels at 4 h p.i. The tumour uptake for both tracers was independent of the tumour volume for all investigated time points. Both tracers showed heterogeneous intra-tumoural distribution.
[(18)F]EF3 tumour uptake reached similar levels at 4 h p.i. compared with tumour retention observed after injection of [(18)F]FMISO at 2 h p.i. Although [(18)F]EF3 is a promising non-invasive tracer, it is not superior over [(18)F]FMISO for the visualisation of tumour hypoxia. No significant differences between [(18)F]EF3 and [(18)F]FMISO were observed with regard to the intra-tumoural distribution and the extra-tumoural tissue retention.
本研究旨在对新型正电子发射断层扫描（PET）缺氧标志物2-(2-硝基咪唑-1-基)-N-(3-[(18)F],3,3-三氟丙基)乙酰胺([(18)F]EF3)与参考缺氧示踪剂[(18)F]氟米索硝唑([(18)F]FMISO)进行定量比较。
每隔2天向两组荷同基因横纹肌肉瘤肿瘤的大鼠分别注射[(18)F]EF3或[(18)F]FMISO。通过在选定组织的图像上绘制感兴趣区域进行体内PET分析。所得活性数据通过每克组织注射放射性百分比(%ID/g)和肿瘤与血液(T/B)比值进行定量。通过对冷冻肿瘤切片进行放射自显影来确定放射性的空间分布。
[(18)F]EF3的血液清除速度比[(18)F]FMISO快。与其他组织相比，两种示踪剂在肿瘤组织中的清除速度均较慢。这导致T/B比值随示踪剂注射后时间(p.i.)的增加而升高。与[(18)F]FMISO的最大摄取量相比，[(18)F]EF3在注射后2小时的肿瘤最大摄取量显著较低，但在注射后4小时达到相似水平。在所有研究时间点，两种示踪剂的肿瘤摄取均与肿瘤体积无关。两种示踪剂在肿瘤内均表现出异质性分布。
与[(18)F]FMISO在注射后2小时观察到的肿瘤滞留情况相比，[(18)F]EF3在注射后4小时的肿瘤摄取量达到相似水平。尽管[(18)F]EF3是一种有前景的非侵入性示踪剂，但在肿瘤缺氧可视化方面并不优于[(18)F]FMISO。在肿瘤内分布和肿瘤外组织滞留方面，未观察到[(18)F]EF3和[(18)F]FMISO之间存在显著差异。
