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可光激活染料磺化酞菁氯铝在荷可移植性肿瘤小鼠体内的组织摄取、分布及效能

Tissue uptake, distribution, and potency of the photoactivatable dye chloroaluminum sulfonated phthalocyanine in mice bearing transplantable tumors.

作者信息

Chan W S, Marshall J F, Lam G Y, Hart I R

机构信息

Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London, United Kingdom.

出版信息

Cancer Res. 1988 Jun 1;48(11):3040-4.

PMID:3284641
Abstract

The potency of chloroaluminum sulfonated phthalocyanine (ClAlSPc) as a photosensitizing agent for photodynamic therapy of cancer was evaluated in vivo by its ability to be taken up and retained by murine tumors of diverse histological origin. Antitumor effects following laser irradiation were evaluated by measurement of the tumor weights of dissected-out tumor masses. Three tumors (Colo 26, a colorectal carcinoma; M5076, a reticulum cell sarcoma; and UV-2237, a fibrosarcoma) growing s.c. in the flank region retained substantially greater quantities of ClAlSPc than did adjacent skin and muscle achieving peak values 24-48 h after the i.v. administration of ClAlSPc (10 mg/kg). The relative magnitude of ClAlSPc retention by these tumors was Colo 26 greater than M5076 greater than UV-2237. However, normal liver and spleen were organs which retained the greatest amounts of ClAlSPc even compared to the s.c. grown tumors and other normal tissues examined. Flow cytometric analysis of tumor cell suspensions obtained from collagenase-digested tumors showed that individual neoplastic cells were capable of taking up and retaining ClAlSPc. Photodynamic therapy, undertaken by i.v. administration of dye (5 mg/kg) followed 24 h later by local laser light irradiation (675 nm, 100 J), brought about significant (Colo 26, M5076, and 3LL tumors) and obvious but nonsignificant (UV-2237 tumor) reductions in tumor weights, as assessed 5 days later. Thus, selective tumor retention of ClAlSPc coupled with a significant response to red light produced dramatic alterations in cancer growth.

摘要

通过研究氯铝磺化酞菁(ClAlSPc)被不同组织学来源的小鼠肿瘤摄取和保留的能力,在体内评估了其作为癌症光动力治疗光敏剂的效力。通过测量切除肿瘤块的重量来评估激光照射后的抗肿瘤效果。三种在侧腹区域皮下生长的肿瘤(结肠26,一种结肠直肠癌;M5076,一种网状细胞肉瘤;UV - 2237,一种纤维肉瘤)比相邻的皮肤和肌肉保留了大量更多的ClAlSPc,在静脉注射ClAlSPc(10 mg/kg)后24 - 48小时达到峰值。这些肿瘤对ClAlSPc的保留相对量为:结肠26大于M5076大于UV - 2237。然而,正常肝脏和脾脏是保留ClAlSPc量最大的器官,甚至与皮下生长的肿瘤和检查的其他正常组织相比也是如此。对从胶原酶消化的肿瘤中获得的肿瘤细胞悬液进行流式细胞术分析表明,单个肿瘤细胞能够摄取和保留ClAlSPc。光动力治疗通过静脉注射染料(5 mg/kg),24小时后进行局部激光照射(675 nm,100 J),5天后评估发现,肿瘤重量有显著降低(结肠26、M5076和3LL肿瘤)以及明显但不显著的降低(UV - 2237肿瘤)。因此,ClAlSPc在肿瘤中的选择性保留以及对红光的显著反应导致了癌症生长的显著改变。

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