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在神经母细胞瘤小鼠模型中,用于疾病进展早期检测和监测的体内生物发光成像。

In vivo bioluminescence imaging for early detection and monitoring of disease progression in a murine model of neuroblastoma.

作者信息

Dickson Paxton V, Hamner Blair, Ng Catherine Y C, Hall Marshall M, Zhou Junfang, Hargrove Phillip W, McCarville M Beth, Davidoff Andrew M

机构信息

Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

出版信息

J Pediatr Surg. 2007 Jul;42(7):1172-9. doi: 10.1016/j.jpedsurg.2007.02.027.

DOI:10.1016/j.jpedsurg.2007.02.027
PMID:17618876
Abstract

BACKGROUND

We evaluated the potential of bioluminescence imaging (BLI) for early tumor detection, demonstrating occult sites of disseminated disease and assessing disease progression in a murine model of neuroblastoma.

METHODS

Neuroblastoma cells engineered to express the enzyme firefly luciferase were used to establish localized tumors and disseminated disease in SCID mice. Bioluminescent signal intensity was measured at serial time points, and compared with traditional methods of evaluating tumor growth.

RESULTS

Bioluminescence imaging detected subcutaneous and retroperitoneal tumors weeks before they were palpable or appreciable by ultrasound. Bioluminescent signal intensity at both sites then paralleled tumor growth. After intravenous administration of tumor cells, BLI revealed disseminated disease in the liver, lungs, and bone marrow, again weeks before any gross disease was present. The presence of tumor within these sites at early time points was confirmed by reverse transcriptase-polymerase chain reaction. Finally, BLI permitted a real-time, noninvasive, quantitative method for following response to therapy in a model of minimal residual disease.

CONCLUSION

Bioluminescence imaging detects tumor much earlier than traditional methods. In addition, it can detect, quantify, and follow micrometastasis in real-time during disease progression. This methodology is extremely valuable for studying tumor tissue tropism, mechanisms of metastasis, and response to therapy in murine tumor models.

摘要

背景

我们评估了生物发光成像(BLI)在神经母细胞瘤小鼠模型中进行早期肿瘤检测、显示播散性疾病隐匿部位以及评估疾病进展的潜力。

方法

利用经基因工程改造以表达萤火虫荧光素酶的神经母细胞瘤细胞,在严重联合免疫缺陷(SCID)小鼠中建立局部肿瘤和播散性疾病模型。在连续时间点测量生物发光信号强度,并与评估肿瘤生长的传统方法进行比较。

结果

生物发光成像在皮下和腹膜后肿瘤可触及或超声可检测到数周前就检测到了它们。然后,两个部位的生物发光信号强度与肿瘤生长情况平行。静脉注射肿瘤细胞后,BLI显示肝脏、肺和骨髓中存在播散性疾病,同样也是在出现任何肉眼可见疾病数周之前。通过逆转录聚合酶链反应证实了这些部位在早期时间点存在肿瘤。最后,在微小残留病模型中,BLI提供了一种实时、非侵入性的定量方法来跟踪治疗反应。

结论

生物发光成像比传统方法能更早地检测到肿瘤。此外,它可以在疾病进展过程中实时检测、量化和跟踪微转移。这种方法对于研究小鼠肿瘤模型中的肿瘤组织嗜性、转移机制和治疗反应极具价值。

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