Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging
Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging
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DOI：
10.1038/sj.neo.7900121
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发表时间：
2000-11-01
期刊：
影响因子：
4.8
通讯作者：
Ross, BD
中科院分区：
文献类型：
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作者：
Rehemtulla, A;Stegman, LD;Ross, BD
目前对动物原位肿瘤模型的评估利用生存作为主要治疗终点。体内生物发光成像（BLI）是一种快速且易于使用的敏感成像方式，可能是评估抗肿瘤治疗的理想工具[1]。使用组成型表达荧光素酶的人类肿瘤细胞系，在腹膜内 [2]、皮下和血管内 [3] 癌症模型中评估了肿瘤生长动力学和对治疗的反应。然而，尚未证实使用这种方法来评估原位肿瘤模型。在本报告中，研究了 BLI 无创定量原位大鼠脑肿瘤的生长和治疗诱导的细胞杀伤的能力，这些肿瘤源自经过基因工程改造以稳定表达萤火虫荧光素酶 (9L(Luc)) 的 9L 胶质肉瘤细胞。通过分别使用低温冷却 CCD 相机和磁共振成像 (MRI) 定量光子发射和肿瘤体积，监测随时间推移的脑内肿瘤负荷。检测到的光子数和肿瘤体积之间存在极好的相关性（r=0.91）。对 1,3-双(2-氯乙基)-1-亚硝基脲 (BCNU) 治疗后连续 MRI 体积测量和 BLI 光子计数确定的肿瘤细胞杀伤进行定量比较，结果表明两种成像方式产生的细胞杀伤值具有统计学相似性 (P=.951)。这些结果直接验证了 BLI 成像作为评估活体动物抗肿瘤治疗的强大定量工具。
Current assessment of orthotopic tumor models in animals utilizes survival as the primary therapeutic end point. In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating antineoplastic therapies [1]. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tumor growth and response to therapy have been assessed in intraperitoneal [2], subcutaneous, and intravascular [3] cancer models. However, use of this approach for evaluating orthotopic tumor models has not been demonstrated. In this report, the ability of BLI to noninvasively quantitate the growth and therapeutic-induced cell kill of orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically engineered to stably express firefly luciferase (9L(Luc)) was investigated. Intracerebral tumor burden was monitored over time by quantitation of photon emission and tumor volume using a cryogenically cooled CCD camera and magnetic resonance imaging (MRI), respectively. There was excellent correlation (r=0.91) between detected photo ns and tu mor volume. A quantitative comparison of tumor cell kill determined from serial MRI volume measurements and BLI photon counts following 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment revealed that both imaging modalities yielded statistically similar cell kill values (P=.951). These results provide direct validation of BLI imaging as a powerful and quantitative tool for the assessment of antineoplastic therapies in living animals.