Quantifying initial cellular events of mouse radiation lymphomagenesis and its tumor prevention in vivo by positron emission tomography and magnetic resonance imaging
Quantifying initial cellular events of mouse radiation lymphomagenesis and its tumor prevention in vivo by positron emission tomography and magnetic resonance imaging
复制标题
通过正电子发射断层扫描和磁共振成像量化小鼠放射性淋巴瘤发生的初始细胞事件及其体内肿瘤预防
DOI：
10.1016/j.molonc.2014.11.009
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
and Saga T
中科院分区：
文献类型：
--
作者：
Hasegawa S;Morokoshi Y;Tsuji A B;Kokubo T;Aoki I;Furukawa T;Zhang M-R;and Saga T
小鼠辐射诱导的胸腺淋巴瘤（RITL）是通过分次全身X射线照射（FX）诱导的，已成为研究辐射致癌作用的有用模型。在该模型中，胸腺和骨髓（BM）中的初始辐射后细胞事件对于肿瘤发生至关重要，并且BM移植（BMT）防止RITL。然而，这些事件的直接评估是迄今为止的非侵入性监测技术的缺乏限制。在这里，我们已经开发了正电子发射断层扫描（PET）和磁共振成像（MRI）的方法来量化的RITL发展和BMT在活体动物的影响的关键事件。根据扩散加权MRI计算表观扩散系数（ADC），以评价接受FX的小鼠BM的变化。ADC值显着改变，在照射的BM，对应于照射的BM的病理结果，恢复到正常水平后BMT比自发恢复。PET与4 <$-[甲基-11 C]硫代胸苷，一种新的示踪剂细胞增殖，显示照射胸腺显示显着较高的示踪剂摄取比未照射胸腺1周后FX。有趣的是，其增加的摄取被BMT完全消除，即使在胸腺中有非常少的供体来源的细胞。此后，胸腺接受BMT显着增加示踪剂摄取。这些发现表明BMT首先抑制FX诱导的胸腺细胞异常增殖，然后加速胸腺再生。本研究证明了使用PET和MRI在辐射诱发癌症的动物模型中无创监测致瘤细胞过程的可行性。
Radiation-induced thymic lymphoma (RITL) in mice is induced by fractionated whole-body X-irradiation (FX) and has served as a useful model for studying radiation carcinogenesis. In this model, the initial postirradiation cellular events in the thymus and bone marrow (BM) are critically important for tumorigenesis, and BM transplantation (BMT) prevents RITL. However, direct assessment of these events is so far restricted by the lack of noninvasive monitoring techniques. Here, we have developed positron emission tomography (PET) and magnetic resonance imaging (MRI) methods to quantify the events critical for RITL development and the effects of BMT in living animals. Apparent diffusion coefficients (ADCs) were calculated from diffusion-weighted MRI to evaluate the changes in the BM of mice receiving FX. ADC values dramatically changed in the irradiated BM, corresponding to pathological findings of the irradiated BM, returning to normal levels following BMT sooner than with spontaneous recovery. PET with 4ʹ-[methyl-11C]thiothymidine, a novel tracer for cell proliferation, revealed that the irradiated thymus showed significantly higher tracer uptake than the unirradiated thymus 1 week after FX. Interestingly, its increased uptake was completely abolished by BMT, even with very few donor-derived cells in the thymus. Thereafter, the thymus receiving BMT had significantly increased tracer uptake. These findings suggest that BMT first suppresses FX-induced aberrant thymocyte proliferation and then accelerates thymic regeneration. This study demonstrates the feasibility of using PET and MRI for noninvasive monitoring of tumorigenic cellular processes in an animal model of radiation-induced cancer.