Rehemtulla A, Stegman L D, Cardozo S J, Gupta S, Hall D E, Contag C H, Ross B D
The Center for Molecular Imaging and the Department of Radiation Oncology,University of Michigan Medical School, Ann Arbor, MI 48109-0648, USA.
Neoplasia. 2000 Nov-Dec;2(6):491-5. doi: 10.1038/sj.neo.7900121.
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. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tumor growth and response to therapy have been assessed in intraperitoneal, and subcutaneous, and intravascular 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 (9LLuc) 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 photons and tumor 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.
目前对动物原位肿瘤模型的评估将生存期作为主要治疗终点。体内生物发光成像（BLI）是一种灵敏的成像方式，快速且易于操作，可能是评估抗肿瘤治疗的理想工具。利用组成性表达荧光素酶的人肿瘤细胞系，已在腹腔内、皮下和血管内癌症模型中评估了肿瘤生长动力学及对治疗的反应。然而，尚未证明该方法可用于评估原位肿瘤模型。在本报告中，研究了BLI对源自经基因工程改造以稳定表达萤火虫荧光素酶（9LLuc）的9L胶质肉瘤细胞的原位大鼠脑肿瘤生长和治疗诱导的细胞杀伤进行无创定量的能力。分别使用低温冷却的电荷耦合器件（CCD）相机和磁共振成像（MRI）通过光子发射定量和肿瘤体积测量随时间监测脑内肿瘤负荷。检测到的光子与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）治疗后通过连续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，结果显示两种成像方式产生的细胞杀伤值在统计学上相似（P = 0.951）。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的有效性。
