The effect of fluence rate on tumor and normal tissue responses to photodynamic therapy

The effect of fluence rate on tumor and normal tissue responses to photodynamic therapy
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DOI:
10.1111/j.1751-1097.1998.tb05228.x
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发表时间:
1998-04-01
影响因子:
3.3
通讯作者:
Henderson, BW
Henderson, BW
中科院分区:
生物学3区
文献类型:
--
作者:
Sitnik, TM;Henderson, BW

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在低注量率下进行的光动力疗法(PDT)可能会增强肿瘤反应并影响治疗选择性。我们使用Photofrin(R) (5 mg/kg)研究了注量率对小鼠辐射诱导纤维肉瘤(RIF)对PDT反应的影响,在大范围的注量率(10-200 mW/cm(2))和注量(25-378 J/ cm(2))下测试了肿瘤反应,低注量率更有效;需要类似于 10 mW/cm(2) 下的 60 J/cm(2) 的功率才能实现与 150 mW/cm(2) 下的 100 J/cm(2) 类似的肿瘤生长延迟以及类似于 200 mW/cm(2) 下的 150 J/cm(2) 的肿瘤生长延迟。尽管效率有所提高,但较低的注量率仍需要更长的治疗时间才能达到同等的抗肿瘤效果:10 mW/cm(2) 下 57 J/cm(2) 需要 95 分钟,而 150 mW/cm(2) 下 100 J/cm(2) 需要 11 分钟。通过小鼠 (C3H) 足部对 Photofrin(R) PDT 的反应,检查注量率对 PDT 对正常组织毒性的影响。采用产生同等肿瘤反应的条件进行治疗,即 10 mW/cm(2) 下 57 J/cm(2) 和 150 mW/cm(2) 下 100 J/cm(2),在较高注量率下会导致更严重的足部反应(中位峰值反应: 10 mW/cm(2) 时为 0.9,150 mW/cm(2) 时为 1.5),组织恢复正常需要更多时间(10 mW/cm(2) 时为 8 天,150 mW/cm(2) 时至少为 30 天)。然而,当足部在不同注量率下以 100 J/cm(2) 的同等注量进行治疗时,较低注量率的治疗会带来较长的愈合时间。总体而言,本文证明较低的 PDT 注量率与肿瘤反应效率的提高相关。如果这种效率的提高是通过降低治疗注量来解释的,则较低的注量率也可能导致正常组织对治疗的更有利的反应。
Photodynamic therapy (PDT), carried out at low fluence rates, may enhance tumor response as well as affect treatment selectivity. We have studied the effects of fluence rate on the response of the murine radiation-induced fibrosarcoma (RIF) to PDT using Photofrin(R) (5 mg/kg), Tumor response was tested over a large range of fluence rates (10-200 mW/cm(2)) and fluences (25-378 J/ cm(2)), Low fluence rates were more efficient; similar to 60 J/cm(2) at 10 mW/cm(2) was needed to achieve the same tumor growth delay as similar to 100 J/cm(2) at 150 mW/cm(2) and similar to 150 J/cm(2) at 200 mW/cm(2). Despite this increased efficiency, lower fluence rates still required longer treatment times for equivalent anti-tumor effects: 95 min for 57 J/cm(2) at 10 mW/cm(2) versus 11 min for 100 J/cm(2) at 150 mW/cm(2). Effects of fluence rate on the PDT toxicity to normal tissue were examined through the response of the murine (C3H) foot to Photofrin(R) PDT, Treatment with conditions that produced equivalent tumor responses, i,e, 57 J/cm(2) at 10 mW/cm(2) and 100 J/cm(2) at 150 mW/cm(2), resulted in a more severe foot response at the higher fluence rate (median peak response: 0.9 at 10 mW/cm(2), 1.5 at 150 mW/cm(2)) with more time required for tissue to return to normal (8 days at 10 mW/cm(2), at least 30 days at 150 mW/cm(2)). However, when feet were treated with an equal fluence of 100 J/cm(2) at various fluence rates, longer healing times accompanied the lower fluence rate treatments. Overall, this paper demonstrates that lower PDT fluence rates are associated with increased efficiency of tumor response. If this increased efficiency is accounted for by lowering treatment fluence, lower fluence rates also may result in a more favorable normal tissue response to treatment.