Efficacy of 5-Aminolevulinic Acid in Photodynamic Detection and Photodynamic Therapy in Veterinary Medicine

被引:32
作者
Osaki, Tomohiro [1 ]
Yokoe, Inoru [1 ]
Sunden, Yuji [1 ]
Ota, Urara [2 ]
Ichikawa, Tomoki [2 ]
Imazato, Hideo [2 ]
Ishii, Takuya [2 ]
Takahashi, Kiwamu [2 ]
Ishizuka, Masahiro [2 ]
Tanaka, Tohru [2 ]
Li, Liming [3 ]
Yamashita, Masamichi [1 ]
Murahata, Yusuke [1 ]
Tsuka, Takeshi [1 ]
Azuma, Kazuo [1 ]
Ito, Norihiko [1 ]
Imagawa, Tomohiro [1 ]
Okamoto, Yoshiharu [1 ]
机构
[1] Tottori Univ, Fac Agr, Joint Dept Vet Clin Med, 4-101 Koyama Minami, Tottori 6808553, Japan
[2] SBI Pharmaceut Co Ltd, Tokyo 1066020, Japan
[3] Chitose Inst Sci & Technol, Dept Bio & Mat Photon, Chitose 0660012, Japan
来源
CANCERS | 2019年 / 11卷 / 04期
关键词
5-aminolevulinic acid; carcinoma; cat; dog; protoporphyrin IX; sarcoma; TRANSITIONAL-CELL CARCINOMA; PROTOPORPHYRIN-IX FLUORESCENCE; BLADDER-CANCER; GUIDED RESECTION; DIAGNOSIS; FERROCHELATASE; SURGERY; TUMORS; LIGHT; ALA;
D O I
10.3390/cancers11040495
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
5-Aminolevulinic acid (5-ALA), a commonly used photosensitizer in photodynamic detection (PDD) and therapy (PDT), is converted in situ to the established photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. To extend 5-ALA-PDT application, we evaluated the PpIX fluorescence induced by exogenous 5-ALA in various veterinary tumors and treated canine and feline tumors. 5-ALA-PDD sensitivity and specificity in the whole sample group for dogs and cats combined were 89.5 and 50%, respectively. Notably, some small tumors disappeared upon 5-ALA-PDT. Although single PDT application was not curative, repeated PDT+/-chemotherapy achieved long-term tumor control. We analyzed the relationship between intracellular PpIX concentration and 5-ALA-PDT in vitro cytotoxicity using various primary tumor cells and determined the correlation between intracellular PpIX concentration and 5-ALA transporter and metabolic enzyme mRNA expression levels. 5-ALA-PDT cytotoxicity in vitro correlated with intracellular PpIX concentration in carcinomas. Ferrochelatase mRNA expression levels strongly negatively correlated with PpIX accumulation, representing the first report of a correlation between mRNA expression related to PpIX accumulation and PpIX concentration in canine tumor cells. Our findings suggested that the results of 5-ALA-PDD might be predictive for 5-ALA-PDT therapeutic effects for carcinomas, with 5-ALA-PDT plus chemotherapy potentially increasing the probability of tumor control in veterinary medicine.
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页数:18
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