Chang S C, MacRobert A J, Bown S G
National Medical Laser Centre, University College London Medical School, England, UK.
J Urol. 1996 May;155(5):1744-8.
Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Problems of detrusor muscle scarring and prolonged cutaneous photosensitivity with current photosensitizers may be reduced by using the new photosensitizer precursor, 5-aminolevulinic acid (ALA). We studied the fluorescence distribution of protoporphyrin IX (PpIX, the active derivative of ALA) in rat urinary bladder after intravesical administration of ALA as the first step to undertaking PDT using locally administered ALA.
Solutions of varying concentrations of ALA and pH were given intravesically to Wistar rats. The bladder was removed 1 to 24 hours later for measurement of the tissue levels of PpIX by fluorescence microscopy in the layers of the bladder wall.
The stability of the ALA solution steadily decreased as the pH was increased from 2.1 to 7. The best value was pH 5.5, at which the stability of the solution and the urothelial tolerance were both acceptable. The maximum PpIX fluorescence intensity ratio between urothelium and the underlying muscle layer was 11 to 1. This was seen 5 hours after instillation of 1% ALA solution at pH 5.5. A 10% ALA solution gave higher levels of PpIX in the urothelium, but less selectivity between layers.
Under appropriate conditions, intravesical instillation of ALA can be used to sensitize the bladder urothelium with a ratio between urothelial and muscle concentrations of PpIX of up to 11:1.
光动力疗法（PDT）在浅表性膀胱肿瘤治疗方面具有巨大潜力。使用新型光敏剂前体5-氨基乙酰丙酸（ALA）或许可以减少目前光敏剂所导致的逼尿肌瘢痕形成和皮肤光敏性延长的问题。作为使用局部给药ALA进行PDT的第一步，我们研究了ALA膀胱内给药后大鼠膀胱中原卟啉IX（PpIX，ALA的活性衍生物）的荧光分布。
将不同浓度和pH值的ALA溶液膀胱内注入Wistar大鼠。1至24小时后取出膀胱，通过荧光显微镜测量膀胱壁各层组织中PpIX的水平。
随着pH值从2.1增加到7，ALA溶液的稳定性稳步下降。最佳pH值为5.5，此时溶液稳定性和尿路上皮耐受性均可接受。尿路上皮与下层肌肉层之间的最大PpIX荧光强度比为11比1。这一比例在pH值为5.5的1%ALA溶液灌注5小时后可见。10%的ALA溶液使尿路上皮中的PpIX水平更高，但各层之间的选择性较低。
在适当条件下，膀胱内灌注ALA可用于使膀胱尿路上皮致敏，尿路上皮与肌肉中PpIX浓度之比可达11:1。
