Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
J Nucl Med. 2012 May;53(5):823-30. doi: 10.2967/jnumed.111.101808. Epub 2012 Apr 9.
Noninvasive in vivo imaging of biologic processes using PET is an important tool in preclinical studies. We observed significant differences in 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-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 (18)F-FLT tracer uptake.
We injected arthritic, healthy, and CT26 colon carcinoma-bearing mice with (18)F-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 (18)F-FLT uptake before the 10-min static PET measurements. For dynamic PET scans, mice were anesthetized during the entire measurement. (18)F-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 (18)F-FLT injection and after PET measurement to analyze pH, carbon dioxide partial pressure (pCO(2)), and lactate values.
A significantly reduced (18)F-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 (18)F-FLT uptake. Breathing air completely abolished this phenomenon. Analysis of blood samples that were obtained from the mice before (18)F-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 (18)F-FLT uptake, as reflected by increased pCO(2) and reduced pH and lactate values.
Oxygen-breathing conscious mice sustained respiratory acidosis and, consequently, reduced cell proliferation and (18)F-FLT uptake in arthritic ankles and CT26 colon carcinomas. Thus, we suggest the use of air instead of oxygen breathing for (18)F-FLT PET measurements.
使用正电子发射断层扫描术对生物过程进行非侵入性活体成像，是临床前研究中的一个重要工具。当我们用氧气让患关节炎的老鼠和携带 CT26 结肠癌的老鼠呼吸时，我们观察到关节炎踝关节和癌之间的 3'-脱氧-3'-(18)F-氟代胸苷（(18)F-FLT）摄取在动态和静态正电子发射断层扫描测量中有显著差异。因此，我们怀疑空气或氧气呼吸和麻醉方案可能会影响(18)F-FLT 示踪剂的摄取。
在进行静态或动态小动物正电子发射断层扫描术之前，我们给患关节炎、健康和携带 CT26 结肠癌的老鼠注射(18)F-FLT。在进行 10 分钟静态正电子发射断层扫描术之前，让自发性吸氧或空气的老鼠在摄取(18)F-FLT 时保持清醒或用氯胺酮和甲苯噻嗪麻醉。对于动态正电子发射断层扫描术，在整个测量过程中，老鼠都处于麻醉状态。通过在踝关节、癌和肌肉组织周围画感兴趣区域，以每立方厘米注射剂量的百分比报告(18)F-FLT 摄取量。此外，在注射(18)F-FLT 之前和正电子发射断层扫描术之后收集静脉血样，以分析 pH 值、二氧化碳分压（pCO(2)）和乳酸值。
与摄取(18)F-FLT 期间麻醉的老鼠相比，在摄取(18)F-FLT 期间清醒并吸氧的关节炎踝关节和 CT26 结肠癌老鼠中，（18）F-FLT 的摄取量明显减少。呼吸空气完全消除了这种现象。从老鼠身上获得的血液样本分析表明，氧气呼吸和摄取示踪剂时的意识引起呼吸性酸中毒。发现酸中毒是导致（18）F-FLT 摄取减少的主要因素，表现为 pCO(2)升高、pH 值和乳酸值降低。
吸氧的清醒老鼠维持呼吸性酸中毒，从而导致关节炎踝关节和 CT26 结肠癌中的细胞增殖和（18）F-FLT 摄取减少。因此，我们建议在进行(18)F-FLT 正电子发射断层扫描术测量时使用空气而不是氧气呼吸。
