Localization and efficacy analysis of the phototherapeutic lutetium texaphyrin (PCI-0123) in the murine EMT6 sarcoma model

被引:99
作者
Woodburn, KW [1 ]
Fan, Q [1 ]
Miles, DR [1 ]
Kessel, D [1 ]
Luo, Y [1 ]
Young, SW [1 ]
机构
[1] WSU, SCH MED, DEPT PHARMACOL, DETROIT, MI USA
关键词
D O I
10.1111/j.1751-1097.1997.tb08579.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Lutetium texaphyrin (PCI-0123) is a pure, water-soluble photodynamic therapy (PDT) agent that is activated by tissue-penetrating far red light, The sensitizer is highly fluorescent and exhibits a strong, broad emission signal at 750 nm. In vitro cellular uptake studies revealed an increase in sensitizer retention with incubation time, Confocal laser scanning microscopy demonstrated that the intracellular localization site of PCI-0123 is the lysosomes, Ensuing illumination of the EMT6 cells led to lysosomal breakup, extensive cytoplasmic blebbing and subsequent cell death, Noninvasive spectral imaging analysis of PCI-0123 fluorescence depicted selective drug uptake, compared to surrounding normal tissue, in EMT6 mammary sarcomas syngeneic to BALB/c mice. The PCI-0123 PDT was shown to effectively treat the EMT6 murine sarcoma, Irradiation (732 nm light) 3 h postintravenous injection of 10 mu mol PCI-0123 per kg gave 100% cures (no evidence of cancer), whereas light exposure at 5 h resulted in 75% cures, Hematoxylin and eosin histologic examination of photoirradiated tumors indicated apoptosis of the EMT6 neoplasms at early times post-PDT progressing, with time, to extensive necrotic areas, Gel electrophoresis of extracted photoirradiated tumors showed the typical apoptotic DNA ladder pattern that increased in intensity following PDT treatment.
引用
收藏
页码:410 / 415
页数:6
相关论文
共 26 条
[21]  
WOODBURN KW, 1992, PHOTOCHEM PHOTOBIOL, V55, P697
[22]   Influence of drug and light regimens in determining PDT efficacy with lutetium texaphyrin [J].
Woodburn, KW ;
Young, SW ;
Miller, RA .
OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY V, PROCEEDINGS OF, 1996, 2675 :172-178
[23]   Lutetium texaphyrin (PCI-0123): A near-infrared, water-soluble photosensitizer [J].
Young, SW ;
Woodburn, KW ;
Wright, M ;
Mody, TD ;
Fan, Q ;
Sessler, JL ;
Dow, WC ;
Miller, RA .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1996, 63 (06) :892-897
[24]   Gadolinium(III) texaphyrin: A tumor selective radiation sensitizer that is detectable by MRI [J].
Young, SW ;
Qing, F ;
Harriman, A ;
Sessler, JL ;
Dow, WC ;
Mody, TD ;
Hemmi, GW ;
Hao, YP ;
Miller, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (13) :6610-6615
[25]   APOPTOSIS DURING PHOTODYNAMIC THERAPY-INDUCED ABLATION OF RIF-1 TUMORS IN C3H MICE - ELECTRON-MICROSCOPIC, HISTOPATHOLOGIC AND BIOCHEMICAL-EVIDENCE [J].
ZAIDI, SIA ;
OLEINICK, NL ;
ZAIM, MT ;
MUKHTAR, H .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1993, 58 (06) :771-776
[26]   Apoptosis of mouse MS-2 fibrosarcoma cells induced by photodynamic therapy with Zn(II)-phthalocyanine [J].
Zhou, CN ;
Chi, SJ ;
Deng, JS ;
Liang, JL ;
Jori, G ;
Milanesi, C .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1996, 33 (03) :219-223