Mathews Marlon S, Angell-Petersen Even, Sanchez Rogelio, Sun Chung-Ho, Vo Van, Hirschberg Henry, Madsen Steen J
Beckman Laser Institute, University of California, Irvine, California 92612, USA.
Lasers Surg Med. 2009 Oct;41(8):578-84. doi: 10.1002/lsm.20808.
Achieving local control of gliomas with photodynamic therapy (PDT) requires the delivery of adequate light fluences to depths of 1-2 cm in the resection margin where the majority of local recurrences originate. This is clinically impractical with current single-shot, intraoperative PDT treatments due to the length of time required to deliver adequate fluences. Multiple or extended treatment protocols would therefore seem to be required. The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated PDT using single or, repetitive light delivery protocols was investigated at both low and ultra low fluence rates.
STUDY DESIGN/MATERIALS AND METHODS: Human glioma spheroids (400 microm diameter) were subjected to sub-threshold light fluence (1.5, 3, or 6 J cm(-2)) ALA-PDT consisting of four light delivery schemes: single treatment given over either 1 or 24 hours, repetitive treatment given either as four 1 hour light treatments separated by a 4 day interval, or 24 hours light delivery, consisting of four 24 hours treatments separated by a 3 day interval. Treatment efficacy was evaluated using a growth assay. In some cases, confocal microscopy was used to image cell viability.
The repetitive and single light treatment protocols were most effective when delivered at ultra low (microW cm(-2)) fluence rates. In all cases, growth inhibition was light dose-dependent. The repetitive ultra low fluence rate treatment (1.5 J cm(-2); irradiance = 17 microW cm(-2)) light delivery protocol was the most effective resulting in total growth inhibition during the 2-week observation period.
Ultra low light fluence rate ALA-PDT results in significant spheroid growth inhibition. Repeated administration of ALA was required during repetitive and/or protracted single PDT treatment protocols. The existence of a lower fluence rate limit, below which the efficacy of threshold light fluences diminish was not found in these studies. Lasers Surg. Med. 41:578-584, 2009. (c) 2009 Wiley-Liss, Inc.
通过光动力疗法（PDT）实现胶质瘤的局部控制，需要将足够的光通量传递至切除边缘1 - 2厘米深处，而多数局部复发正是源于此处。由于传递足够光通量所需时间较长，目前单次术中PDT治疗在临床上并不实用。因此，似乎需要多次或延长治疗方案。本研究在低和超低光通量率下，研究了人胶质瘤球体对使用单次或重复光传递方案的5 - 氨基酮戊酸（ALA）介导的PDT的反应。
研究设计/材料与方法：人胶质瘤球体（直径400微米）接受亚阈值光通量（1.5、3或6 J/cm²）的ALA - PDT，包括四种光传递方案：单次治疗持续1或24小时，重复治疗为四次1小时光治疗，间隔4天，或24小时光传递，由四次24小时治疗组成，间隔3天。使用生长测定法评估治疗效果。在某些情况下，使用共聚焦显微镜对细胞活力进行成像。
当以超低（微瓦/平方厘米）光通量率进行传递时，重复和单次光治疗方案最为有效。在所有情况下，生长抑制均呈光剂量依赖性。重复超低光通量率治疗（1.5 J/cm²；辐照度 = 17微瓦/平方厘米）光传递方案最为有效，在2周观察期内导致完全生长抑制。
超低光通量率ALA - PDT导致球体生长显著抑制。在重复和/或延长单次PDT治疗方案期间需要重复给予ALA。在这些研究中未发现存在更低的光通量率下限，低于该下限阈值光通量的疗效会降低。《激光外科与医学》41:578 - 584，2009年。（c）2009威利 - 利斯公司
