氧敏感 MRI：肿瘤放疗反应的预测性影像生物标志物？
Oxygen-Sensitive MRI: A Predictive Imaging Biomarker for Tumor Radiation Response?
机构信息
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas.
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
出版信息
Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1519-1529. doi: 10.1016/j.ijrobp.2021.03.039. Epub 2021 Mar 26.
PURPOSE
To develop a noninvasive prognostic imaging biomarker related to hypoxia to predict SABR tumor control.
METHODS AND MATERIALS
A total of 145 subcutaneous syngeneic Dunning prostate R3327-AT1 rat tumors were focally irradiated once using cone beam computed tomography guidance on a small animal irradiator at 225 kV. Various doses in the range of 0 to 100 Gy were administered, while rats breathed air or oxygen, and tumor control was assessed up to 200 days. Oxygen-sensitive magnetic resonance imaging (MRI) (T-weighted, ΔR, ΔR*) was applied to 79 of these tumors at 4.7 T to assess response to an oxygen gas breathing challenge on the day before irradiation as a probe of tumor hypoxia.
RESULTS
Increasing radiation dose in the range of 0 to 90 Gy enhanced tumor control of air-breathing rats with a TCD estimated at 59.6 ± 1.5 Gy. Control was significantly improved at some doses when rats breathed oxygen during irradiation (eg, 40 Gy; P < .05), and overall there was a modest left shift in the control curve: TCD(oxygen) = 53.1 ± 3.1 Gy (P < .05 vs air). Oxygen-sensitive MRI showed variable response to oxygen gas breathing challenge; the magnitude of T-weighted signal response (%ΔSI) allowed stratification of tumors in terms of local control at 40 Gy. Tumors showing %ΔSI >0.922 with O-gas breathing challenge showed significantly better control at 40 Gy during irradiation while breathing oxygen (75% vs 0%, P < .01). In addition, increased radiation dose (50 Gy) substantially overcame resistance, with 50% control for poorly oxygenated tumors. Stratification of dose-response curves based on %ΔSI >0.922 revealed different survival curves, with TCD = 36.2 ± 3.2 Gy for tumors responsive to oxygen gas breathing challenge; this was significantly less than the 54.7 ± 2.4 Gy for unresponsive tumors (P < .005), irrespective of the gas inhaled during tumor irradiation.
CONCLUSIONS
Oxygen-sensitive MRI allowed stratification of tumors in terms of local control at 40 Gy, indicating its use as a potential predictive imaging biomarker. Increasing dose to 50 Gy overcame radiation resistance attributable to hypoxia in 50% of tumors.
目的
开发一种与缺氧相关的无创预后成像生物标志物，以预测 SABR 肿瘤控制。
方法与材料
共对 145 个皮下同源性 Dunning 前列腺 R3327-AT1 大鼠肿瘤进行了研究，使用小动物辐照仪在锥形束 CT 引导下对每个肿瘤进行单次聚焦照射。照射范围为 0 至 100 Gy，同时大鼠呼吸空气或氧气，并在 200 天内评估肿瘤控制情况。对其中 79 个肿瘤在 4.7 T 下进行了氧敏感磁共振成像（MRI）（T 加权，ΔR，ΔR*）检查，以评估辐照前一天吸氧时的氧合状态变化作为肿瘤缺氧的探针。
结果
在 0 至 90 Gy 的范围内增加放射剂量，使呼吸空气的大鼠的肿瘤控制得到增强，TCD 估计值为 59.6±1.5 Gy。当大鼠在照射期间呼吸氧气时，在某些剂量下控制明显改善（例如 40 Gy；P<.05），并且整体上控制曲线向左略有偏移：TCD（氧气）=53.1±3.1 Gy（P<.05 与空气相比）。氧敏感 MRI 显示出对氧合气体呼吸挑战的不同反应；T 加权信号反应的幅度（%ΔSI）允许根据 40 Gy 时的局部控制对肿瘤进行分层。在呼吸氧气时接受 O 气体呼吸挑战的肿瘤显示出 %ΔSI>0.922，显示出显著更好的 40 Gy 时的控制率（75%对 0%，P<.01）。此外，增加剂量（50 Gy）可显著克服缺氧肿瘤的耐药性，对低氧肿瘤的控制率为 50%。基于 %ΔSI>0.922 对剂量反应曲线进行分层，显示出不同的生存曲线，对氧合气体呼吸挑战有反应的肿瘤的 TCD=36.2±3.2 Gy；这显著低于对氧合气体呼吸挑战无反应的肿瘤的 54.7±2.4 Gy（P<.005），而与肿瘤照射期间吸入的气体无关。
结论
氧敏感 MRI 允许根据 40 Gy 时的局部控制对肿瘤进行分层，表明其可作为潜在的预测性成像生物标志物。将剂量增加到 50 Gy 可克服 50%肿瘤因缺氧引起的放射抵抗。
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