Heterogeneity in intratumor correlations of 18F-FDG, 18F-FLT, and 61Cu-ATSM PET in canine sinonasal tumors.
Heterogeneity in intratumor correlations of 18F-FDG, 18F-FLT, and 61Cu-ATSM PET in canine sinonasal tumors.
复制标题
DOI：
10.2967/jnumed.113.121921
复制
发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Jeraj R
中科院分区：
文献类型：
--
作者：
Bradshaw TJ;Bowen SR;Jallow N;Forrest LJ;Jeraj R
肿瘤内生物学特性的异质性和不同表型之间的关系可能对生物靶向治疗提出挑战。了解不同肿瘤类型的不同表型之间的关系有助于指导治疗选择。这项研究的目的是描述两种组织学类型的肿瘤中糖代谢、增殖和缺氧的空间相关性。用18F-FDG、18F-标记的39-脱氧-39-氟代胸苷(18F-Flt)和~(61)Cu标记的双乙酰-双(N4-甲基氨基硫脲)(~(61)Cu-ATSM)PET/CT对20例自发性鼻腔肿瘤(13例癌和7例肉瘤)犬进行了连续3天的显像。精确的定位和固定技术，再加上麻醉，可以实现可重复定位的静止扫描。用Mann-Whitney U检验比较肉瘤和癌体积的标准摄取值(SUV)。将患者图像严格配准在一起，并比较肿瘤内示踪剂摄取的分布。使用基于体素的Spearman相关系数来量化示踪剂间的相关性，并比较肉瘤和癌的相关系数。3种示踪剂的最高摄取体积的相对重叠被量化，并将肉瘤和癌症的值进行比较。在SUV测量和表型相关性中观察到了很大程度的异质性。肿瘤和肉瘤在SUV测量方面有显著差异，肿瘤的18F-FDG最大SUV显著高于肉瘤(11.1比5.0；P=0.01)，以及更高的61Cu-ATSM平均SUV(2.6比1.2；P=0.02)。在18F-FDG和18F-Flt(0.80vs.0.61；P=0.02)、18F-Flt和61Cu-ATSM(0.83vs.0.38；P<；0.0001)和18F-FDG和61Cu-ATSM(0.82vs.0.69；P=0.04)的比较中，癌的总体平均Spearman相关系数显著高于肉瘤(0.80vs.0.61；P=0.02)。此外，3种示踪剂的最高摄取体积在肿瘤中的重叠程度明显高于肉瘤。葡萄糖代谢、增殖和缺氧的关系在不同的肿瘤中是不同的，癌症往往具有高度的相关性，而肉瘤的相关性较低。因此，犬癌肿瘤是针对单一生物学特性的治疗的强有力的靶点，而肉瘤肿瘤可能不太适合这样的治疗。组织学特定的PET相关性对生物靶标定义的稳健性具有深远的影响。
Intratumor heterogeneity in biologic properties and in relationships between various phenotypes may present a challenge for biologically targeted therapies. Understanding the relationships between different phenotypes in individual tumor types could help inform treatment selection. The goal of this study was to characterize spatial correlations of glucose metabolism, proliferation, and hypoxia in 2 histologic types of tumors. Twenty canine veterinary patients with spontaneously occurring sinonasal tumors (13 carcinomas and 7 sarcomas) were imaged with 18F-FDG, 18F-labeled 39-deoxy-39-fluorothymidine (18F-FLT), and 61Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone) (61Cu-ATSM) PET/CT on 3 consecutive days. Precise positioning and immobilization techniques coupled with anesthesia enabled motionless scans with repeatable positioning. Standardized uptake values (SUVs) of gross sarcoma and carcinoma volumes were compared by use of Mann– Whitney U tests. Patient images were rigidly registered together, and intratumor tracer uptake distributions were compared. Voxel-based Spearman correlation coefficients were used to quantify intertracer correlations, and the correlation coefficients of sarcomas and carcinomas were compared. The relative overlap of the highest uptake volumes of the 3 tracers was quantified, and the values were compared for sarcomas and carcinomas. Large degrees of heterogeneity in SUV measures and phenotype correlations were observed. Carcinoma and sarcoma tumors differed significantly in SUV measures, with carcinoma tumors having significantly higher 18F-FDG maximum SUVs than sarcoma tumors (11.1 vs. 5.0; P = 0.01) as well as higher 61Cu-ATSM mean SUVs (2.6 vs. 1.2; P = 0.02). Carcinomas had significantly higher population-averaged Spearman correlation coefficients than sarcomas in comparisons of 18F-FDG and 18F-FLT (0.80 vs. 0.61; P = 0.02), 18F-FLT and 61Cu-ATSM (0.83 vs. 0.38; P < 0.0001), and 18F-FDG and 61Cu-ATSM (0.82 vs. 0.69; P = 0.04). Additionally, the highest uptake volumes of the 3 tracers had significantly greater overlap in carcinomas than in sarcomas. The relationships of glucose metabolism, proliferation, and hypoxia were heterogeneous across different tumors, with carcinomas tending to have high correlations and sarcomas having low correlations. Consequently, canine carcinoma tumors are robust targets for therapies that target a single biologic property, whereas sarcoma tumors may not be well suited for such therapies. Histology-specific PET correlations have far-reaching implications for the robustness of biologic target definition.
登录
查看更多内容
DOI：
10.1073/pnas.1116227108
发表时间：
2012-01-03
影响因子：
11.1
作者：
Donnelly, Paul S.;Liddell, Jeffrey R.;Crouch, Peter J.
通讯作者：
Crouch, Peter J.
影响因子：
1.2
作者：
Kondo, Yumi;Matsunaga, Satoru;Sasaki, Nobuo
通讯作者：
Sasaki, Nobuo
影响因子：
11.5
作者：
Rajendran, JG;Mankoff, DA;Krohn, KA
通讯作者：
Krohn, KA
影响因子：
11.2
作者：
Baird, K;Davis, S;Meltzer, PS
通讯作者：
Meltzer, PS
影响因子：
3.5
作者：
McCall, Keisha C.;Barbee, David L.;Jeraj, Robert
通讯作者：
Jeraj, Robert