Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate.
Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate.
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DOI：
10.1038/bjc.1998.231
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发表时间：
1998-05
影响因子：
8.8
通讯作者：
Henderson, B W
中科院分区：
文献类型：
--
作者：
Sitnik, T M;Hampton, J A;Henderson, B W
有人提出，在光动力治疗（PDT）过程中产生的O2可能会导致周围肿瘤氧的光化学消耗，从而导致急性缺氧和限制治疗效果。我们研究了在PDT期间和之后，使用5 mg kg（-1）Photofrin和30、75或150 mW cm（-2）的注量率对小鼠RIF肿瘤中pO 2的影响。三个治疗组PDT前的中位pO 2范围为2.9 - 5.2 mmHg。在照射的第一分钟内，中位肿瘤pO 2随所有注量率下降至0.7至1.1 mmHg之间的值。这些影响是迅速和完全可逆的，如果照明中断。在长时间照射（20-50 J cm（-2））期间，pO 2在30 mW cm（-2）能量密度率下恢复到中位数7.4 mmHg，但在150 mW cm（-2）能量密度率下仍保持较低水平（中位数pO 2 1.7 mmHg）。PDT后未发现注量率效应，在30和150 mW cm（-2）下，治疗结束后1-3 h内，肿瘤pO 2中位数从对照水平降至1.0-1.8 mmHg。在30 mW cm（-2）下，100 J cm（-2）PDT比150 mW cm（-2）PDT导致显著（P = 0.0004）更长的中位肿瘤再生长时间，表明较低的注量率可以改善PDT反应。血管灌注研究揭示了正常和肿瘤血管系统反应的显著注量率依赖性差异。这些数据建立了肿瘤pO 2、PDT期间应用的注量率和治疗结果之间的直接关系。这些发现具有直接的临床意义。
It has been proposed that the generation of O2 during photodynamic therapy (PDT) may lead to photochemical depletion of ambient tumour oxygen, thus causing acute hypoxia and limiting treatment effectiveness. We have studied the effects of fluence rate on pO2, in the murine RIF tumour during and after PDT using 5 mg kg(-1) Photofrin and fluence rates of 30, 75 or 150 mW cm(-2). Median pO2 before PDT ranged from 2.9 to 5.2 mmHg in three treatment groups. Within the first minute of illumination, median tumour pO2 decreased with all fluence rates to values between 0.7 and 1.1 mmHg. These effects were rapidly and completely reversible if illumination was interrupted. During prolonged illumination (20-50 J cm(-2)) pO2 recovered at the 30 mW cm(-2) fluence rate to a median value of 7.4 mmHg, but remained low at the 150 mW cm(-2) fluence rate (median pO2 1.7 mmHg). Fluence rate effects were not found after PDT, and at both 30 and 150 mW cm(-2) median tumour pO2 fell from control levels to 1.0-1.8 mmHg within 1-3 h after treatment conclusion. PDT with 100 J cm(-2) at 30 mW cm(-2) caused significantly (P = 0.0004) longer median tumour regrowth times than PDT at 150 mW cm(-2), indicating that lower fluence rate can improve PDT response. Vascular perfusion studies uncovered significant fluence rate-dependent differences in the responses of the normal and tumour vasculature. These data establish a direct relationship between tumour pO2, the fluence rate applied during PDT and treatment outcome. The findings are of immediate clinical relevance.