Datta S N, Loh C S, MacRobert A J, Whatley S D, Matthews P N
Department of Urology, University Hospital of Wales, Cardiff, UK.
Br J Cancer. 1998 Oct;78(8):1113-8. doi: 10.1038/bjc.1998.637.
Photodynamic therapy is a potential treatment for superficial bladder cancer that utilizes photosensitizer drugs, which are activated by light to cause tissue destruction. However, first-generation photosensitizers cause prolonged phototoxicity, have poor tumour specificity and can accumulate within detrusor muscle, resulting in permanent loss of bladder capacity following treatment. A newer drug, called 5-aminolaevulinic acid (ALA), generates a sensitizer called protoporphyrin IX (PpIX) in situ and has been shown, qualitatively, to be more tumour specific. The fluorescence kinetics of ALA-induced PpIX was investigated in patient biopsies of bladder tumour, normal urothelium and detrusor muscle, both in vitro after incubation of specimens in ALA-rich culture medium for various times and in vivo after instillation of intravesical ALA before endoscopic resection. The fluorescence in tumour tissue was twice that of normal urothelium in vitro and up to tenfold in vivo. There was little ALA-induced fluorescence in detrusor muscle, both in vitro and in vivo. Most importantly, no patients experienced phototoxicity or other adverse events following intravesical instillation of ALA.
光动力疗法是浅表性膀胱癌的一种潜在治疗方法，它利用光敏药物，这些药物被光激活后会导致组织破坏。然而，第一代光敏剂会引起长时间的光毒性，肿瘤特异性差，且会在逼尿肌中蓄积，导致治疗后膀胱容量永久性丧失。一种名为5-氨基乙酰丙酸（ALA）的新型药物可原位生成一种名为原卟啉IX（PpIX）的敏化剂，并且从定性角度来看，已证明其具有更高的肿瘤特异性。对膀胱肿瘤、正常尿路上皮和逼尿肌的患者活检组织中ALA诱导的PpIX的荧光动力学进行了研究，包括将标本在富含ALA的培养基中孵育不同时间后的体外研究，以及在内镜切除术前膀胱内灌注ALA后的体内研究。肿瘤组织中的荧光在体外是正常尿路上皮的两倍，在体内高达十倍。在体外和体内，逼尿肌中几乎没有ALA诱导的荧光。最重要的是，膀胱内灌注ALA后，没有患者出现光毒性或其他不良事件。
