T Osaki, I Yokoe, Y Sunden, U Ota, T Ichikawa… – Cancers, 2019
Abstract
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.
… The dogs and cats were orally administered 5-ALA HCl at a dose of 40 mg/kg 4 h prior to biopsy or surgery. Generally, butorphanole (0.2 mg/kg) and midazolam (0.15 mg/kg) were administered as pre-anesthetic agents and general anesthesia was induced with intravenous propofol (4 mg/kg), and then maintained with isoflurane and oxygen after tracheal intubation. Furthermore, robenacoxib (Onsior®, Elanco Japan, Tokyo, Japan) was administered subcutaneously at a dose of 2 mg/kg as an analgesic agent. After excision of 141 masses with surrounding normal tissues, the masses were further incised through the midline and the non-necrotic areas were fluoresced using an LED light source at 405 nm. The video camera (HDR-CX180, SONY, Tokyo, Japan) was equipped with a long-pass filter designed to block blue light (for observation of fluorescence). For fluorescence spectrometry, LED405-SMA-TI (Thorlabs Japan Inc., Tokyo, Japan), R600-8-UV–VIS-SR (StellarNet, Tampa, FL, USA), and Black-Comet CXR-50 TEC spectrometers (StellarNet) were used to obtain the spectra for each tissue. The maximum fluorescence peak of PpIX was at approximately 635 nm. The PDD protocol was approved by the Ethics Committee at the Faculty of Agriculture, Tottori University (ethical approval number: H28-003).
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