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

Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, Japan
SBI Pharmaceuticals Co., Ltd., Tokyo 106-6020, Japan
Department of Bio- and Material Photonics, Chitose Institute of Science and Technology, Chitose 066-0012, Japan
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 495;
Received: 20 March 2019 / Revised: 3 April 2019 / Accepted: 5 April 2019 / Published: 7 April 2019
(This article belongs to the Special Issue Photodynamic Therapy (PDT) in Oncology)
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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. View Full-Text
Keywords: 5-aminolevulinic acid; carcinoma; cat; dog; protoporphyrin IX; sarcoma 5-aminolevulinic acid; carcinoma; cat; dog; protoporphyrin IX; sarcoma

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Osaki, T.; Yokoe, I.; Sunden, Y.; Ota, U.; Ichikawa, T.; Imazato, H.; Ishii, T.; Takahashi, K.; Ishizuka, M.; Tanaka, T.; Li, L.; Yamashita, M.; Murahata, Y.; Tsuka, T.; Azuma, K.; Ito, N.; Imagawa, T.; Okamoto, Y. Efficacy of 5-Aminolevulinic Acid in Photodynamic Detection and Photodynamic Therapy in Veterinary Medicine. Cancers 2019, 11, 495.

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