Hirschberg Henry, Uzal Francisco A, Chighvinadze David, Zhang Michelle J, Peng Qian, Madsen Steen J
Beckman Laser Institute, University of California, Irvine, California 92612, USA.
Lasers Surg Med. 2008 Oct;40(8):535-42. doi: 10.1002/lsm.20670.
Photodynamic therapy (PDT) is a local antineoplastic treatment with the potential for tumor cell specificity. PDT using either hematoporphyrin derivatives or 5-aminolevulinic acid (ALA) has been reported to induce brain edema indicating disruption of the blood-brain barrier (BBB). We have evaluated the ability of ALA-mediated PDT to open the BBB in rats. This will permit access of chemotherapeutic agents to brain tumor cells remaining in the resection cavity wall, but limit their penetration into normal brain remote from the site of illumination.
STUDY DESIGN/MATERIALS AND METHODS: ALA-PDT was performed on non-tumor bearing inbred Fischer rats at increasing fluence levels. Contrast T(1)-weighted high field (3 T) magnetic resonance imaging (MRI) scans were used to monitor the degree of BBB disruption which could be inferred from the intensity and volume of the contrast agent visualized.
PDT at increasing fluence levels between 9 and 26 J demonstrated an increasing contrast flow rate. A similar increased contrast volume was observed with increasing fluence rates. The BBB was found to be disrupted 2 hours following PDT and 80-100% restored 72 hours later at the lowest fluence level. No effect on the BBB was observed if 26 J of light was given in the absence of ALA.
ALA-PDT was highly effective in opening the BBB in a localized region of the brain. The degradation of the BBB was temporary in nature at fluence levels of 9 J, opening rapidly following treatment and significantly restored during the next 72 hours. No signs of tissue damage were seen on histological sections at this fluence level. However, higher fluences did demonstrate permanent tissue changes localized in the immediate vicinity of the light source.
光动力疗法（PDT）是一种具有肿瘤细胞特异性潜力的局部抗肿瘤治疗方法。据报道，使用血卟啉衍生物或5-氨基酮戊酸（ALA）的光动力疗法会诱发脑水肿，提示血脑屏障（BBB）遭到破坏。我们评估了ALA介导的光动力疗法在大鼠中打开血脑屏障的能力。这将使化疗药物能够进入残留在切除腔壁中的脑肿瘤细胞，但限制它们渗透到远离光照部位的正常脑组织中。
研究设计/材料与方法：对无肿瘤的近交系Fischer大鼠进行不同光通量水平的ALA-光动力疗法。使用对比增强T1加权高场（3T）磁共振成像（MRI）扫描来监测血脑屏障破坏程度，这可通过所观察到的造影剂强度和体积来推断。
在9至26焦耳之间逐渐增加光通量水平的光动力疗法显示出对比剂流速增加。随着光通量率增加，观察到类似的造影剂体积增加。在光动力疗法后2小时发现血脑屏障被破坏，在最低光通量水平下，72小时后恢复80 - 100%。如果在没有ALA的情况下给予26焦耳的光照，则未观察到对血脑屏障有影响。
ALA-光动力疗法在打开脑局部区域的血脑屏障方面非常有效。在9焦耳的光通量水平下，血脑屏障的降解本质上是暂时的，治疗后迅速打开，并在接下来的72小时内显著恢复。在此光通量水平下，组织学切片上未见到组织损伤迹象。然而，更高的光通量确实显示出在光源紧邻区域出现永久性组织变化。
