Inoue Yusuke, Tojo Arinobu, Sekine Rieko, Soda Yasushi, Kobayashi Seiichiro, Nomura Akiko, Izawa Kiyoko, Kitamura Toshio, Okubo Toshiyuki, Ohtomo Kuni
Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Eur J Nucl Med Mol Imaging. 2006 May;33(5):557-65. doi: 10.1007/s00259-005-0048-4.
The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells.
Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage.
The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells.
Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity.
将体内生物发光成像应用于肿瘤模型的非侵入性定量监测，依赖于生物发光强度与肿瘤负荷之间的正相关关系。我们进行了细胞培养研究，以探讨小鼠白血病模型细胞中生物发光信号强度与活细胞数量之间的关系。
将依赖白细胞介素-3（IL-3）的小鼠前B细胞系Ba/F3用萤火虫荧光素酶转导，以产生在逆转录病毒长末端重复序列控制下稳定表达荧光素酶的细胞。将表达荧光素酶的细胞用p190 BCR-ABL转导，使其能够不依赖因子进行增殖。将细胞在各种条件下培养，并将生物发光信号强度与活细胞数量及细胞周期阶段进行比较。
在用荧光素酶和p190 BCR-ABL转导后，Ba/F3细胞表现出自主生长以及稳定的荧光素酶表达，并且体内生物发光成像能够对植入小鼠体内的这些细胞进行外部检测。在细胞培养研究中，生物发光强度倾向于反映细胞增殖情况以及对伊马替尼的反应。然而，每个活细胞的发光受到依赖因子细胞中IL-3浓度以及不依赖因子细胞中增殖阶段和伊马替尼浓度的影响，从而损害了活细胞数量与生物发光信号强度之间的比例关系。每个细胞的发光倾向于随着增殖细胞的比例而变化。
尽管体内生物发光成像能够对白血病模型动物进行非侵入性监测，但环境因素和治疗干预可能会导致肿瘤负荷与生物发光强度之间出现一些差异。
