Inoue Yusuke, Izawa Kiyoko, Kiryu Shigeru, Kobayashi Seiichiro, Tojo Arinobu, Ohtomo Kuni
Department of Radiology, Institute of Medical Science, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Exp Hematol. 2008 Dec;36(12):1634-41. doi: 10.1016/j.exphem.2008.08.004. Epub 2008 Oct 25.
We investigated the utility of in vivo bioluminescence imaging (BLI) in assessing the therapeutic effects of total body irradiation (TBI) in a murine hematological malignancy model.
The suspension of Ba/F3 cells transduced with firefly luciferase and p190 BCR-ABL genes was exposed to ionizing radiation, and viable cell numbers and bioluminescent signals were measured serially. Mice intravenously inoculated with the cells underwent TBI at various doses. In vivo BLI was performed repeatedly until spontaneous death, and whole-body bioluminescence signals were determined as an indicator of whole-body tumor burden.
In the cell culture study, bioluminescence signals generally reflected viable cell numbers, despite some overestimation immediately after irradiation. Sublethal TBI in mice transiently depressed the increase in whole-body signals and prolonged survival. Spontaneous death occurred at similar signal levels regardless of radiation dose. A significant negative correlation was found between survival and whole-body signal early after TBI. Significant dose dependence was demonstrated for both survival and signal increase early after TBI and was more evident for signal increase. Lethally irradiated mice without bone marrow transplantation died while showing weak signals. In mice receiving lethal TBI and syngeneic bone marrow transplantation, signal reduction and prolongation of survival were prominent, and whole-body signals at death were similar to those in nonirradiated or sublethally irradiated mice.
In vivo BLI allows longitudinal, quantitative evaluation of the response to TBI in mice of a hematological malignancy model. Antitumor effects can be assessed early and reliably using in vivo BLI.
我们研究了体内生物发光成像（BLI）在评估小鼠血液系统恶性肿瘤模型中全身照射（TBI）治疗效果方面的实用性。
将转导了萤火虫荧光素酶和p190 BCR-ABL基因的Ba/F3细胞悬液暴露于电离辐射下，连续测量存活细胞数量和生物发光信号。给静脉接种这些细胞的小鼠进行不同剂量的TBI。反复进行体内BLI直至小鼠自然死亡，并将全身生物发光信号作为全身肿瘤负荷的指标进行测定。
在细胞培养研究中，尽管照射后立即存在一些高估情况，但生物发光信号总体上反映了存活细胞数量。小鼠接受亚致死剂量的TBI后，全身信号的增加暂时受到抑制，生存期延长。无论辐射剂量如何，小鼠在相似的信号水平下自然死亡。TBI后早期，生存期与全身信号之间存在显著的负相关。TBI后早期，生存期和信号增加均表现出显著的剂量依赖性，且信号增加更为明显。接受致死剂量照射但未进行骨髓移植的小鼠在发出微弱信号时死亡。在接受致死剂量TBI和同基因骨髓移植的小鼠中，信号降低和生存期延长显著，死亡时的全身信号与未照射或接受亚致死剂量照射的小鼠相似。
体内BLI可对血液系统恶性肿瘤模型小鼠对TBI的反应进行纵向、定量评估。使用体内BLI可以早期且可靠地评估抗肿瘤效果。
