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.
Highlights
Photodynamics techniques, which utilize photosensitizers that accumulate preferentially in neoplastic and other hyperproliferative tissues, have been recently introduced to clinical practice for Cancers 2019, 11, 495; doi:10.3390/cancers11040495 www.mdpi.com/journal/cancersCancers 2019, 11, 495 both detection and therapeutic purposes
In order to extend the range of application of 5-Aminolevulinic acid (5-ALA)-photodynamic therapy (PDT), we evaluated 5-ALA-photodynamic detection (PDD)
In the present study we evaluated the use of 5-ALA-PDD in various veterinary tumors as a screen for 5-ALA-PDT and attempted to extend the range of 5-ALA-PDT application
Summary
Photodynamics techniques, which utilize photosensitizers that accumulate preferentially in neoplastic and other hyperproliferative tissues, have been recently introduced to clinical practice for Cancers 2019, 11, 495; doi:10.3390/cancers11040495 www.mdpi.com/journal/cancersCancers 2019, 11, 495 both detection and therapeutic purposes. Photodynamics techniques, which utilize photosensitizers that accumulate preferentially in neoplastic and other hyperproliferative tissues, have been recently introduced to clinical practice for Cancers 2019, 11, 495; doi:10.3390/cancers11040495 www.mdpi.com/journal/cancers. Photodynamic therapy (PDT) constitutes a novel treatment for cancer and certain-malignant conditions. Photodynamic detection (PDD) involves utilization the fluorescence of a photosensitizer to localize abnormal tissue and reveals neoplastic lesions that cannot be detected by means of conventional methods [6]. PDT and PDD differ with regard to the wavelength of light applied to the tumor cells and tissues. 405 nm) and emit red fluorescence (590–700 nm), whereas in PDT, light administration of approximately 600–800 nm induces phototoxicity and tumor cell death through varying degrees of apoptosis and necrosis [7] In PDD, photosensitizers can be efficiently excited by visible blue light (ca. 405 nm) and emit red fluorescence (590–700 nm), whereas in PDT, light administration of approximately 600–800 nm induces phototoxicity and tumor cell death through varying degrees of apoptosis and necrosis [7]
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