Rhodes L E, Tsoukas M M, Anderson R R, Kollias N
Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard University, Boston, USA.
J Invest Dermatol. 1997 Jan;108(1):87-91. doi: 10.1111/1523-1747.ep12285644.
Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) is increasingly employed for skin cancer, yet ALA dosing is crude. Using iontophoresis, we developed a rapid and quantifiable system for topical ALA delivery, with measurement of subsequent PpIX fluorescence and phototoxicity. ALA was iontophoresed from a 2% solution into upper inner arm skin of 13 healthy volunteers. Six doses of ALA were delivered with a series of charges varying from 3-120 milliCoulombs (mC); four additional doses were given with a charge of 60 mC. Five hours post-iontophoresis, sites were irradiated with broad-band yellow-red light, the series of six ALA doses receiving 100 J/cm2, while the four identical doses received 6.25, 12.5, 25, and 50 J/cm2, respectively. Resultant erythema was measured by reflectance spectroscopy. The time course of PpIX fluorescence was ALA-dose-dependent. With charge < or = 24 mC, PpIX fluorescence peaked at 3 h and returned to zero at 9-10 h, whereas charges > 24 mC had a sustained peak at 5-10 h, falling to zero by 24 h. Pre-irradiation, PpIX fluorescence correlated with ALA dose (r = 1.0). PpIX fluorescence fell immediately post-irradiation (p < 0.0001); recovery levels at 3 h correlated with ALA dose (p < 0.0001). Delayed erythema correlated with ALA dose and irradiation dose (p < 0.0001, p < 0.01, respectively). Both PpIX fluorescence intensity pre-irradiation and fall in PpIX fluorescence post-irradiation correlated with erythema (r = 0.98). Hence, PpIX synthesis is ALA-dose-dependent, and phototoxicity can be predicted from ALA dose, irradiation dose, and photobleaching of PpIX. This reproducible system allows accurate dosimetry in topical PDT and facilitates study of ALA metabolism.
局部应用5-氨基酮戊酸（ALA）的光动力疗法（PDT）在皮肤癌治疗中的应用日益广泛，但ALA的给药方式比较粗放。我们利用离子导入技术，开发了一种用于局部递送ALA的快速且可量化的系统，并对随后的原卟啉IX（PpIX）荧光和光毒性进行测量。将ALA从2%的溶液通过离子导入法导入13名健康志愿者的上臂内侧皮肤。通过一系列3至120毫库仑（mC）的电荷输送六剂ALA；另外四剂给予60 mC的电荷。离子导入后5小时，用宽带黄红光照射皮肤部位，六剂ALA系列接受100 J/cm²的照射，而四剂相同剂量的ALA分别接受6.25、12.5、25和50 J/cm²的照射。通过反射光谱法测量产生的红斑。PpIX荧光的时间进程取决于ALA剂量。当电荷≤24 mC时，PpIX荧光在3小时达到峰值，并在9至10小时恢复到零，而电荷>24 mC时，在5至10小时有一个持续的峰值，到24小时降至零。照射前，PpIX荧光与ALA剂量相关（r = 1.0）。照射后PpIX荧光立即下降（p < 0.0001）；3小时时的恢复水平与ALA剂量相关（p < 0.0001）。延迟红斑与ALA剂量和照射剂量相关（分别为p < 0.0001，p < 0.01）。照射前PpIX荧光强度和照射后PpIX荧光下降均与红斑相关（r = 0.98）。因此，PpIX的合成取决于ALA剂量，并且可以根据ALA剂量、照射剂量和PpIX的光漂白来预测光毒性。这个可重复的系统允许在局部PDT中进行精确的剂量测定，并有助于研究ALA的代谢。
