Amano T, Prout G R, Lin C W
Urology Service, Massachusetts General Hospital, Boston 02114.
J Urol. 1988 Feb;139(2):392-5. doi: 10.1016/s0022-5347(17)42441-4.
Photodynamic therapy (PDT) with hematoporphyrin derivative (HpD) as the photosensitizer is a promising new cancer treatment. The major drawback of this procedure is the resulting skin photosensitivity. Patients must remain in subdued light for four to six weeks to avoid cutaneous phototoxicity. In this study, we examine the possibility of reducing the skin photosensitization while maintaining the tumor phototoxic effect by administering the drug directly into the tumor. A subcutaneously implanted mouse bladder tumor (MBT-2) was used. HpD was administered either intraperitoneally (I.P.; 20 mg./kg. b.w.) or by intratumor injection (I.T.; 0.4 mg./cc tumor). The concentrations of HpD in tumor and various tissues (skin, muscle, liver, spleen, kidney, bladder and whole blood) were analyzed at various times after the injection, by 3H-HpD method and by a fluorometric method. Results indicated that at three to 96 hours after the administration, porphyrin levels in tumor were about three to 15 times higher by I.T. than by I.P. injection, while the concentrations in skin and other tissues were 1.3 to 10 times lower. Consequently, at 24 hours after injection ratios between tumor to skin porphyrin were 14 to 92 times higher for I.T. than I.P. injection. Higher porphyrin levels in tumor and lower in normal tissues would indicate lower skin photosensitivity, systemic cytotoxicity and possible greater tumor photosensitivity. This method of porphyrin administration may be useful for the PDT of certain single lesions that are accessible for direct injection.
以血卟啉衍生物(HpD)作为光敏剂的光动力疗法(PDT)是一种很有前景的新型癌症治疗方法。该疗法的主要缺点是会导致皮肤光敏性。患者必须在昏暗光线下停留四至六周以避免皮肤光毒性。在本研究中,我们研究了通过将药物直接注入肿瘤来降低皮肤光敏性同时保持肿瘤光毒性作用的可能性。使用皮下植入的小鼠膀胱肿瘤(MBT - 2)。通过腹腔注射(I.P.;20毫克/千克体重)或瘤内注射(I.T.;0.4毫克/立方厘米肿瘤)给予HpD。在注射后的不同时间,通过³H - HpD法和荧光法分析肿瘤及各种组织(皮肤、肌肉、肝脏、脾脏、肾脏、膀胱和全血)中HpD的浓度。结果表明,给药后三至96小时,瘤内注射时肿瘤中的卟啉水平比腹腔注射高约三至15倍,而皮肤和其他组织中的浓度则低1.3至10倍。因此,注射后24小时,瘤内注射时肿瘤与皮肤卟啉的比率比腹腔注射高14至92倍。肿瘤中较高的卟啉水平和正常组织中较低的卟啉水平表明皮肤光敏性较低、全身细胞毒性较低且可能具有更高的肿瘤光敏性。这种卟啉给药方法可能对某些可直接注射的单个病变的光动力疗法有用。