Nuclear Medicine and Radiotherapy, Henri Becquerel Cancer Center and Rouen University Hospital, and QuantIF-LITIS (EA [Equipe d'Accueil] 4108), Faculty of Medicine, University of Rouen, Rouen, France.
J Nucl Med. 2013 Sep;54(9):1543-50. doi: 10.2967/jnumed.112.118083. Epub 2013 Aug 5.
As the preparation phase of a multicenter clinical trial using (18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG), (18)F-fluoromisonidazole ((18)F-FMISO), and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in non-small cell lung cancer (NSCLC) patients, we investigated whether 18 nuclear medicine centers would score tracer uptake intensity similarly and define hypoxic and proliferative volumes for 1 patient and we compared different segmentation methods.
Ten (18)F-FDG, ten (18)F-FMISO, and ten (18)F-FLT PET/CT examinations were performed before and during curative-intent radiotherapy in 5 patients with NSCLC. The gold standards for uptake intensity and volume delineation were defined by experts. The between-center agreement (18 nuclear medicine departments connected with a dedicated network, SFMN-net [French Society of Nuclear Medicine]) in the scoring of uptake intensity (5-level scale, then divided into 2 levels: 0, normal; 1, abnormal) was quantified by κ-coefficients (κ). The volumes defined by different physicians were compared by overlap and κ. The uptake areas were delineated with 22 different methods of segmentation, based on fixed or adaptive thresholds of standardized uptake value (SUV).
For uptake intensity, the κ values between centers were, respectively, 0.59 for (18)F-FDG, 0.43 for (18)F-FMISO, and 0.44 for (18)F-FLT using the 5-level scale; the values were 0.81 for (18)F-FDG and 0.77 for both (18)F-FMISO and (18)F-FLT using the 2-level scale. The mean overlap and mean κ between observers were 0.13 and 0.19, respectively, for (18)F-FMISO and 0.2 and 0.3, respectively, for (18)F-FLT. The segmentation methods yielded significantly different volumes for (18)F-FMISO and (18)F-FLT (P < 0.001). In comparison with physicians, the best method found was 1.5 × maximum SUV (SUVmax) of the aorta for (18)F-FMISO and 1.3 × SUVmax of the muscle for (18)F-FLT. The methods using the SUV of 1.4 and the method using 1.5 × the SUVmax of the aorta could be used for (18)F-FMISO and (18)F-FLT. Moreover, for (18)F-FLT, 2 other methods (adaptive threshold based on 1.5 or 1.6 × muscle SUVmax) could be used.
The reproducibility of the visual analyses of (18)F-FMISO and (18)F-FLT PET/CT images was demonstrated using a 2-level scale across 18 centers, but the interobserver agreement was low for the (18)F-FMISO and (18)F-FLT volume measurements. Our data support the use of a fixed threshold (1.4) or an adaptive threshold using the aorta background to delineate the volume of increased (18)F-FMISO or (18)F-FLT uptake. With respect to the low tumor-on-background ratio of these tracers, we suggest the use of a fixed threshold (1.4).
在使用（18）F-氟代脱氧葡萄糖（（18）F-FDG）、（18）F-氟米索硝唑（（18）F-FMISO）和 3'-脱氧-3' -（18）F-氟胸苷（（18）F-FLT）对非小细胞肺癌（NSCLC）患者进行多中心临床试验的准备阶段，我们研究了 18 个核医学中心是否会对示踪剂摄取强度进行类似评分，并为 1 名患者定义缺氧和增殖体积，我们比较了不同的分割方法。
在 5 名 NSCLC 患者接受根治性放疗前和放疗期间进行了 10 次（18）F-FDG、10 次（18）F-FMISO 和 10 次（18）F-FLT PET/CT 检查。摄取强度的金标准由专家定义。通过κ系数（κ）量化了 18 个核医学部门（通过专用网络 SFMN-net [法国核医学学会] 连接）之间在评分摄取强度（5 级量表，然后分为 2 个级别：0，正常；1，异常）方面的中心间一致性。不同医生定义的体积通过重叠和κ进行比较。摄取区域根据标准化摄取值（SUV）的固定或自适应阈值，用 22 种不同的分割方法进行勾画。
对于摄取强度，中心之间的κ值分别为（18）F-FDG 的 0.59、（18）F-FMISO 的 0.43 和（18）F-FLT 的 0.44，使用 5 级量表；（18）F-FDG 的值为 0.81，（18）F-FMISO 和（18）F-FLT 的值均为 0.77，使用 2 级量表。（18）F-FMISO 和（18）F-FLT 之间观察者的平均重叠和平均κ分别为 0.13 和 0.19，0.2 和 0.3。分割方法为（18）F-FMISO 和（18）F-FLT 生成了显著不同的体积（P < 0.001）。与医生相比，发现最好的方法是（18）F-FMISO 的主动脉最大 SUV（SUVmax）的 1.5 倍和（18）F-FLT 的肌肉 SUVmax 的 1.3 倍。可以使用 SUV 为 1.4 的方法和使用主动脉 SUVmax 的 1.5 倍的方法来测量（18）F-FMISO 和（18）F-FLT。此外，对于（18）F-FLT，还可以使用另外 2 种方法（基于 1.5 或 1.6×肌肉 SUVmax 的自适应阈值）。
在使用 18 个中心的 2 级量表对（18）F-FMISO 和（18）F-FLT PET/CT 图像的视觉分析进行了重现性验证，但（18）F-FMISO 和（18）F-FLT 体积测量的观察者间一致性较低。我们的数据支持使用固定阈值（1.4）或使用主动脉背景的自适应阈值来勾画（18）F-FMISO 或（18）F-FLT 摄取增加的体积。鉴于这些示踪剂的肿瘤与背景的低比值，我们建议使用固定阈值（1.4）。
