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

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.

5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study

“…The in vitro study by White et al [35] analyzed human osteosarcoma cells treated with 5-ALA exposed to either 40-nM excitation wavelength light or kept in the dark for 24 h. Their results showed maximal human osteosarcoma cell death in the light-exposed group with approximately 60-70% cell viability as opposed to more than 90% viability in the dark group. Finally, consistent with the current study results, findings from a more recent report on a variety of carcinomas and sarcomas demonstrated in vitro cytotoxicity and fluorescence in response to 5-ALA application; however, this was noted in veterinary tumors, none of which included myxofibrosarcoma [36]. This veterinary study reported a sensitivity of 89% and a specificity of 50% for red fluorescence across 144 resected tumors.…”

Photodynamic detection of a feline meningioma using 5-aminolaevulinic acid hydrochloride

“…This was analysed by highperformance liquid chromatography (HPLC) using a Capcell Pak C18 UG120 column (5 μm, 4.6 × 150 mm; Shiseido), mobile phase of acetonitrile-10 mM tetrabutylammonium hydroxide solution (pH 7.5) (70:30 by volume; flow rate, 1.0 ml/min; elution temperature, 40°C) and fluorescence detector (excitation 400 nm, emission 630 nm), as described previously. 12 The intratumour PpIX protein concentration was 16.8 nmol/g. For histopathological examination, sample pieces of surgically removed tissue and the cranial bone were formalin-fixed and submitted for histopathology.…”

Nanomaterials for cancer therapy: current progress and perspectives

“…PDT and PTT are two treatment methods related to optical interference. In PDT, a photosensitizer is accumulated in cancerous sites; when irradiated with certain wavelength light, singlet oxygen and other cytotoxic reactive oxygen materials are generated, causing apoptosis and/or necrosis [ 22 ]. PTT uses materials that possess high photothermal conversion efficiency to elevate the temperature of targeted cancerous areas, leading to cancer cell death.…”