Exploration of Imaging Biomarkers for Metabolically-Targeted Osteosarcoma Therapy in a Murine Xenograft Model.
Exploration of Imaging Biomarkers for Metabolically-Targeted Osteosarcoma Therapy in a Murine Xenograft Model.
复制标题
小鼠异种移植模型中代谢靶向骨肉瘤治疗的成像生物标志物的探索。
DOI：
10.1089/cbr.2022.0090
复制
发表时间：
2023
影响因子：
3.4
通讯作者：
LeBlanc,AmyK
中科院分区：
文献类型：
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作者：
Huang,Shan;Ren,Ling;Beck,JessicaA;Phelps,TimE;Olkowski,Colleen;Ton,Anita;Roy,Jyoti;White,MargaretE;Adler,Stephen;Wong,Karen;Cherukuri,Aswini;Zhang,Xiang;Basuli,Falguni;Choyke,PeterL;Jagoda,ElaineM;LeBlanc,AmyK
背景：骨肉瘤（OS）是一种侵袭性儿童癌症，治疗需求尚未得到满足。谷氨酰胺酶1 （GLS1）抑制，单独和联合二甲双胍，破坏肿瘤进展和转移的生物能量需求，显示出临床转化的希望。材料与方法：在MG63.3人OS异种移植小鼠模型中，研究了三种正电子发射断层扫描（PET）临床显像剂[18F]氟-2-脱氧-2-d -葡萄糖（[18F]FDG）、3 ' -[18F]氟-3 ' -脱氧胸腺嘧啶（[18F]FLT）和(2S, 4R)-4-[18F]氟谷氨酰胺（[18F]GLN）作为GLS1选择性抑制剂（CB-839, telaglenastat）和二甲双胍单独或联合治疗7 d后的伴生成像生物标志物。在治疗前后收集肿瘤和参考组织的成像和生物分布数据。结果：药物治疗改变了所有三种PET药物的肿瘤摄取。替格列司他治疗后，FDG的相对摄取量[18F]显著下降，但对照组和单用二甲双胍组则没有。[18F]FLT肿瘤摄取似乎与肿瘤大小呈负相关。治疗后的FLT成像[18F]显示耀斑效应的证据。替格列司他对肿瘤和正常组织中GLN摄取有广泛影响[18F]。结论：推荐基于图像的肿瘤体积量化用于该胫骨肿瘤模型。[18F]FLT和[18F]GLN的表现受肿瘤大小的影响。[18F]FDG可用于检测替格列司他对糖酵解的影响。需要探索动力学示踪剂摄取方案，以确定接受替格lenastat患者GLN摄取的临床相关模式[18F]。
Background:Osteosarcoma (OS) is an aggressive pediatric cancer with unmet therapeutic needs. Glutaminase 1 (GLS1) inhibition, alone and in combination with metformin, disrupts the bioenergetic demands of tumor progression and metastasis, showing promise for clinical translation.Materials and Methods:Three positron emission tomography (PET) clinical imaging agents, [18F]fluoro-2-deoxy-2-D-glucose ([18F]FDG), 3′-[18F]fluoro-3′-deoxythymidine ([18F]FLT), and (2S, 4R)-4-[18F]fluoroglutamine ([18F]GLN), were evaluated in the MG63.3 human OS xenograft mouse model, as companion imaging biomarkers after treatment for 7 d with a selective GLS1 inhibitor (CB-839, telaglenastat) and metformin, alone and in combination. Imaging and biodistribution data were collected from tumors and reference tissues before and after treatment.Results:Drug treatment altered tumor uptake of all three PET agents. Relative [18F]FDG uptake decreased significantly after telaglenastat treatment, but not within control and metformin-only groups. [18F]FLT tumor uptake appears to be negatively affected by tumor size. Evidence of a flare effect was seen with [18F]FLT imaging after treatment. Telaglenastat had a broad influence on [18F]GLN uptake in tumor and normal tissues.Conclusions:Image-based tumor volume quantification is recommended for this paratibial tumor model. The performance of [18F]FLT and [18F]GLN was affected by tumor size. [18F]FDG may be useful in detecting telaglenastat's impact on glycolysis. Exploration of kinetic tracer uptake protocols is needed to define clinically relevant patterns of [18F]GLN uptake in patients receiving telaglenastat.