Quantification of Oxygen Depletion During FLASH Irradiation In Vitro and In Vivo.
Quantification of Oxygen Depletion During FLASH Irradiation In Vitro and In Vivo.
复制标题
体外和体内闪光辐照期间氧消耗的定量。
DOI：
10.1016/j.ijrobp.2021.03.056
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发表时间：
2021-09-01
期刊：
影响因子：
--
通讯作者：
Pogue BW
中科院分区：
文献类型：
--
作者：
Cao X;Zhang R;Esipova TV;Allu SR;Ashraf R;Rahman M;Gunn JR;Bruza P;Gladstone DJ;Williams BB;Swartz HM;Hoopes PJ;Vinogradov SA;Pogue BW
最近已经证明，与肿瘤组织相比，以1000剂量率递送辐射（称为FLASH）优先使正常组织免受辐射损伤。然而，这种现象的潜在机制仍然未知，其中一个最广泛考虑的假设是，该效应与FLASH时的大量氧消耗有关，从而改变照射期间的放射化学损伤，导致正常和肿瘤细胞的不同辐射反应。通过在FLASH照射期间和之后直接测量体内组织氧，可以进一步验证这一假设。氧测量进行了体外和体内使用磷光猝灭法和水溶性分子探针Oxyphor 2 P。每单位剂量的氧变化（G值）被量化，以响应于10 MeV电子束在超高剂量率（UHDR）达到300戈伊/s或常规放射治疗剂量率为0.1戈伊/s的照射。在23°C下使用5% BSA溶液的体外实验中，常规辐照的耗氧量G值为0.19-0.21 mmHg/戈伊（0.34-0.37 μM/戈伊），UHDR辐照的耗氧量G值为0.16-0.17 mmHg/戈伊（0.28-0.30 μM/戈伊）。在体内，在20戈伊的单次FLASH照射后，正常组织中的氧的总降低为2.3±0.3 mmHg，肿瘤组织中的氧的总降低为1.0±0.2 mmHg，p值< 0.00001，而在常规模式下施加的20戈伊的单次照射没有观察到氧的降低。我们的观察结果表明，氧气消耗放射学相关的缺氧水平是不可能发生在散装组织下闪光照射。在体外实验中，相同剂量的闪光灯照射比常规照射引起的耗氧量少，这可能与闪光灯的节约效应有关。然而，FLASH和常规照射之间的氧消耗的差异不能在体内量化，因为常规照射下的氧消耗的测量受到血液中氧再供应的阻碍。
Delivery of radiation at ultrahigh dose rates, known as FLASH, has recently been shown to preferentially spare normal tissues from radiation damage compared to tumor tissues. However, the underlying mechanism of this phenomenon remains unknown, with one of the most widely considered hypothesis being that the effect is related to substantial oxygen depletion upon FLASH, thereby altering the radiochemical damage during irradiation, leading to different radiation responses of normal and tumor cells. Testing of this hypothesis would be advanced by direct measurement of tissue oxygen in vivo during and after FLASH irradiation. Oxygen measurements were performed in vitro and in vivo using the phosphorescence quenching method and a water-soluble molecular probe Oxyphor 2P. The changes in oxygen per unit dose (G-values) were quantified in response to irradiation by 10 MeV electron beam at either ultra-high dose rates (UHDR) reaching 300 Gy/s or conventional radiotherapy dose rates of 0.1 Gy/s. In vitro experiments with 5% BSA solutions at 23°C resulted in G-values for oxygen consumption of 0.19–0.21 mmHg/Gy (0.34–0.37 μM/Gy) for conventional irradiation and 0.16–0.17 mmHg/Gy (0.28–0.30 μM/Gy) for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3±0.3 mmHg in normal tissue and 1.0±0.2 mmHg in tumor tissue with p-value < 0.00001, while no decrease in oxygen was observed from a single fraction of 20 Gy applied in conventional mode. Our observations suggest that oxygen depletion to radiologically relevant levels of hypoxia is unlikely to occur in bulk tissue under FLASH irradiation. For the same dose FLASH irradiation induces less oxygen consumption than conventional irradiation in vitro, which may be related to the FLASH sparing effect. However, the difference in oxygen depletion between FLASH and conventional irradiation could not be quantified in vivo, because measurements of oxygen depletion under conventional irradiation are hampered by resupply of oxygen from the blood.
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影响因子：
5.7
作者：
Montay-Gruel, Pierre;Petersson, Kristoffer;Vozenin, Marie-Catherine
通讯作者：
Vozenin, Marie-Catherine
影响因子：
3.4
作者：
MICHAELS, HB;EPP, ER;PETERSON, EC
通讯作者：
PETERSON, EC
影响因子：
1.4
作者：
Grimes DR;Partridge M
通讯作者：
Partridge M
DOI：
10.1016/0360-3016(86)90224-5
发表时间：
1986-07-01
影响因子：
7
作者：
MICHAELS, HB
通讯作者：
MICHAELS, HB
影响因子：
2.6
作者：
WEISS, H;EPP, ER;SANTOMASSO, A
通讯作者：
SANTOMASSO, A