Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.
The Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada.
Contrast Media Mol Imaging. 2019 Jan 8;2019:6501231. doi: 10.1155/2019/6501231. eCollection 2019.
PURPOSE: The combined use of anatomical magnetic resonance imaging (MRI), cellular MRI, and bioluminescence imaging (BLI) allows for sensitive and improved monitoring of brain metastasis in preclinical cancer models. By using these complementary technologies, we can acquire measurements of viable single cell arrest in the brain after systemic administration, the clearance and/or retention of these cells thereafter, the growth into overt tumours, and quantification of tumour volume and relative cancer cell viability over time. While BLI is very useful in measuring cell viability, some considerations have been reported using cells engineered with luciferase such as increased tumour volume variation, changes in pattern of metastatic disease, and inhibition of tumour growth. PROCEDURES: Here, we apply cellular and anatomical MRI to evaluate growth differences between iron oxide labeled naïve (4T1BR5) and luciferase-expressing (4T1BR5-FLuc-GFP) murine brain-seeking breast cancer cells. Balb/C mice received an intracardiac injection of 20,000 cells and were imaged with MRI on days 0 and 14. Mice that received 4T1BR5-FLuc-GFP cells were also imaged with BLI on days 0 and 14. RESULTS: The number of signal voids in the brain (representing iron-labeled cancer cells) on day 0 was significantly higher in mice receiving 4T1BR5 cells compared to mice receiving 4T1BR5-FLuc-GFP cells ( < 0.0001). Mice that received 4T1BR5 cells also had significantly higher total brain tumour burden and number of brain metastases than mice that received 4T1BR5-FLuc-GFP cells ( < 0.0001). CONCLUSIONS: By employing highly sensitive cellular MRI tools, we demonstrate that engineered cells did not form tumours as well as their naïve counterparts, which appear to primarily be due to a reduction in cell arrest. These results indicate that engineering cancer cells with reporter genes may alter their tropism towards particular organs and highlight another important consideration for research groups that use reporter gene imaging to track metastatic cancer cell fate .
目的：解剖磁共振成像（MRI）、细胞 MRI 和生物发光成像（BLI）的联合使用可敏感且改善临床前癌症模型中脑转移的监测。通过使用这些互补技术，我们可以在全身给药后获得对单个活细胞在大脑中滞留的测量，此后这些细胞的清除和/或保留，以及肿瘤的生长，并随时间定量肿瘤体积和相对癌细胞活力。虽然 BLI 在测量细胞活力方面非常有用，但已经报道了一些使用带有荧光素酶的细胞进行工程的考虑因素，例如肿瘤体积变化增加、转移性疾病模式变化和肿瘤生长抑制。
过程：在这里，我们应用细胞和解剖 MRI 来评估铁标记的幼稚（4T1BR5）和表达荧光素酶的（4T1BR5-FLuc-GFP）鼠脑寻找乳腺癌细胞之间的生长差异。Balb/C 小鼠接受 20,000 个细胞的心脏内注射，并在第 0 天和第 14 天进行 MRI 成像。接受 4T1BR5-FLuc-GFP 细胞的小鼠还在第 0 天和第 14 天进行 BLI 成像。
结果：第 0 天大脑中信号缺失（代表铁标记的癌细胞）的数量在接受 4T1BR5 细胞的小鼠中明显高于接受 4T1BR5-FLuc-GFP 细胞的小鼠（<0.0001）。接受 4T1BR5 细胞的小鼠的总脑肿瘤负担和脑转移数量也明显高于接受 4T1BR5-FLuc-GFP 细胞的小鼠（<0.0001）。
结论：通过使用高度敏感的细胞 MRI 工具，我们证明工程细胞没有像它们的幼稚细胞那样形成肿瘤，这主要是由于细胞滞留减少所致。这些结果表明，用报告基因工程化癌细胞可能会改变它们对特定器官的趋向性，并强调了使用报告基因成像来跟踪转移性癌细胞命运的研究小组的另一个重要考虑因素。
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