Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts
Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts
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DOI：
10.1593/tlo.11316
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发表时间：
2012-04-01
影响因子：
5
通讯作者：
Herman, Joseph M.
中科院分区：
文献类型：
--
作者：
Tuli, Richard;Surmak, Andrew;Herman, Joseph M.
目的：我们报道了一种新的临床前胰腺癌研究模型，该模型使用生物发光成像（BLI）引导照射原位异种移植肿瘤，保留周围正常组织，并定量，无创地纵向评估治疗反应。材料与方法：将表达荧光素酶的MiaPaCa-2胰腺癌细胞原位注射于裸鼠。将BLI与病理肿瘤体积进行比较，并随时间评估光子发射。BLI与正电子发射断层扫描(PET)/计算机断层扫描（CT）相关，以估计肿瘤尺寸。使用BLI和锥束CT （CBCT）比较肿瘤质心位置和估计设置误差。采用小动物放射研究平台（SARRP）进行BLI与CBCT融合指导肿瘤照射。通过γ - h2ax染色评估DNA损伤。采用BLI对治疗反应进行纵向监测。结果：生物发光预测肿瘤体积（R = 0.8984），并随时间线性增加，肿瘤负荷增加10倍。BLI与PET/CT及尸检标本大小相关（P < 0.05）。二维BLI质心相对于CBCT精度为3.5 mm。bli引导下照射的胰腺肿瘤γ - h2ax染色呈阳性，而周围正常组织未受影响。对BLI照射肿瘤的纵向评估显示，与对照组相比，肿瘤生长明显延迟20天。结论：我们已经成功地将SARRP应用于一个生物发光的原位临床前胰腺癌模型，以实现无创：1)允许在治疗前识别肿瘤负荷，2)促进图像引导的局灶放射治疗，3)允许肿瘤负荷正常化和治疗反应的纵向评估。
PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by gamma-H2Ax staining. BLI was used to longitudinally monitor treatment response. RESULTS: Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for gamma-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. CONCLUSIONS: We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response.