Oxygen Breathing Affects 3′-Deoxy-3′-18F-Fluorothymidine Uptake in Mouse Models of Arthritis and Cancer
Oxygen Breathing Affects 3′-Deoxy-3′-18F-Fluorothymidine Uptake in Mouse Models of Arthritis and Cancer
复制标题
DOI：
10.2967/jnumed.111.101808
复制
发表时间：
2012-05-01
影响因子：
9.3
通讯作者：
Kneilling, Manfred
中科院分区：
文献类型：
--
作者：
Fuchs, Kerstin;Kukuk, Damaris;Kneilling, Manfred
使用PET对生物过程进行无创体内成像是临床前研究的重要工具。我们观察到，当小鼠呼吸氧气时，动态和静态PET测量中3'-脱氧-3'- f -18-氟胸腺嘧啶（F-18-FLT）在关节炎踝关节和癌中的摄取有显著差异。因此，我们怀疑空气或氧气呼吸和麻醉方案可能影响F-18-FLT示踪剂的摄取。方法：在静态或动态小动物PET测量之前，给患有关节炎、健康和CT26结肠癌的小鼠注射F-18-FLT。在F-18-FLT摄取期间，自发吸氧或呼吸空气的小鼠被氯胺酮和噻嗪麻醉或保持清醒，然后进行10分钟的静态PET测量。对于动态PET扫描，小鼠在整个测量过程中被麻醉。通过绘制脚踝、癌和肌肉组织周围的感兴趣区域，以每立方厘米注射剂量的百分比报告了F-18-FLT的摄取。此外，在注射F-18-FLT前和PET测量后采集静脉血样本，分析pH、二氧化碳分压（pCO(2)）和乳酸值。结果：与在F-18-FLT摄取过程中被麻醉的小鼠相比，在示踪剂摄取过程中，当小鼠呼吸氧气并有意识时，在关节炎踝关节和CT26结肠癌中测量到F-18-FLT的摄取显著减少。呼吸空气完全消除了这种现象。在注射F-18-FLT前和PET扫描后获得的小鼠血液样本分析表明，在示踪剂摄取期间，氧气呼吸和意识引起的呼吸性酸中毒。酸中毒被发现是导致F-18-FLT摄取减少的主要因素，这反映在pCO(2)增加和pH值和乳酸值降低上。结论：氧呼吸意识小鼠持续呼吸性酸中毒，从而减少关节关节炎和CT26结肠癌的细胞增殖和F-18-FLT摄取。因此，我们建议使用空气而不是氧气呼吸的F-18-FLT PET测量。
Noninvasive in vivo imaging of biologic processes using PET is an important tool in preclinical studies. We observed significant differences in 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT) uptake in arthritic ankles and carcinomas between dynamic and static PET measurements when mice breathed oxygen. Thus, we suspected that air or oxygen breathing and the anesthesia protocol might influence F-18-FLT tracer uptake. Methods: We injected arthritic, healthy, and CT26 colon carcinoma bearing mice with F-18-FLT before static or dynamic small-animal PET measurements. The spontaneously oxygen- or air-breathing mice were kept conscious or anesthetized with ketamine and xylazine during F-18-FLT uptake before the 10-min static PET measurements. For dynamic PET scans, mice were anesthetized during the entire measurement. F-18-FLT uptake was reported in percentage injected dose per cubed centimeter by drawing regions of interest around ankles, carcinomas, and muscle tissue. Additionally, venous blood samples were collected before F-18-FLT injection and after PET measurement to analyze pH, carbon dioxide partial pressure (pCO(2)), and lactate values. Results: A significantly reduced F-18-FLT uptake was measured in arthritic ankles and in CT26 colon carcinomas when the mice breathed oxygen and were conscious during tracer uptake, compared with mice that were anesthetized during F-18-FLT uptake. Breathing air completely abolished this phenomenon. Analysis of blood samples that were obtained from the mice before F-18-FLT injection and after the PET scan implicated respiratory acidosis that was induced by oxygen breathing and consciousness during tracer uptake. Acidosis was found to be the primary factor responsible for the reduced F-18-FLT uptake, as reflected by increased pCO(2) and reduced pH and lactate values. Conclusion: Oxygen-breathing conscious mice sustained respiratory acidosis and, consequently, reduced cell proliferation and F-18-FLT uptake in arthritic ankles and CT26 colon carcinomas. Thus, we suggest the use of air instead of oxygen breathing for F-18-FLT PET measurements.