Photodynamic Therapy (PDT) using intratumoral injection of the 5- aminolevulinic acid (5-ALA) for the treatment of eye cancer in cattle

Abstract

A six-year old Holstein cow with an eye cancer (ocular squamous cell carcinoma) involving the third eyelid and conjunctiva was submitted to photodynamic therapy using intratumoral 20% aminolevulinic acid (5-ALA -Aldrich Chemical Company, Milwaukee, USA) and a light emitting diode (LED -VET LED -MMOptics®) with wavelength between 600 and 700 nm, 2 cm diameter circular light beam, power of 150 mW, light dose of 50 J/cm 2 as a source of irradiation. Fifteen days after the experimental procedure we observed about 50% tumor reduction and complete remission after 3 months. Relapse was not observed up to 12 months after the treatment. Although the study only includes one animal not allowing definite conclusions, it indicates that PDT represents a safe and technically feasible approach in the treatment of eye cancer in cattle.

Photodynamic therapy and diagnosis: Principles and comparative aspects

“…One such second-generation photosensitiser is 5-aminolevulinic acid (ALA), a naturally occurring pro-photosensitiser and precursor for the biosynthesis of heme. For therapeutic purposes, ALA is administered topically (Morton et al, 2008(Morton et al, , 2013, orally (Muller and Wilson, 2006), or intralesionally (Hage et al, 2007;Kim et al, 2012) and enters into all cells; although uptake is potentiated by transporters of beta-amino acids and GABA (Rud et al, 2000), highly expressed on some cancer cells and neurons (Zhang et al, 2013). ALA is then metabolised to the red-fluorescent photosensitiser protoporphyrin IX (PpIX, absorption 635 nm) and finally to non-fluorescent heme (Ajioka et al, 2006, Allison andMoghissi 2013a).…”

“…In human patients ALA has been used for the treatment of T cell lymphoma (Coors et al, 2004), basal cell carcinoma (Kim et al, 2012) squamous cell carcinoma (SCC) and other head and neck cancers (Grant, et al, 1993, Morton et al, 1996. In veterinary medicine, ALA has been used to treat SCC in a cow (Hage et al, 2007) and in cats (Bexfield et al, 2008), sarcoids in horses (Gustafson et al, 2004, Golding et al, 2017 and transitional cell carcinoma in dogs (Lucroy et al, 2003a,b). See Tables 1 and 2. The hydrophilic nature of ALA limits its ability to deeply penetrate intact skin and thereby restricts the use of topically applied ALA-PDT to the treatment of superficial diseases, where the tissue structure is disorganised.…”

“…As is the case in human patients, the smaller and less invasive tumours respond best to PDT (Magne et al, 1997). PDT has also been used to treat SCC in dogs (McCaw et al, 2000), horses (Giuliano 2008), a cow (Hage et al, 2007), snakes (Roberts WG et al,1991) and a Great Hornbill (Suedmeyer et al, 2001).…”

“…Experience of intralesional injection of PS is very limited in animals. One study reported PDT in a cow with ocular SCC using intratumoural injection of ALA. A complete response was observed after 3 months and no relapse 12 months after the treatment (Hage et al, 2007). PDT has also been used for treatment of periocular SCC in horses.…”

Photodynamic therapy (PDT) to treat a chronic skin wound in a dog

“…Many methods have been used in the handling of these wounds, from the use of local anti-septic and antibiotics up to systemic antibiotics, however, many of these wounds tend if to become chronic. In recent years researchers have investigated the effect of the photodynamic therapy in the treatment of cancers (Luckroy, 2002;Hage et al 2004 and2007;Qiang et al, 2006), dermatological diseases (Ceburkov and Gollnick, 2000;Qiang et al, 2006), to control infections caused by bacteria (Lambrechts et al 2005, Carvalho et al 2006) and fungi (Bliss et al 2004) , as well as in the treatment of cutaneous wounds (Hamblin et al 2001, Jayasree et al 2001). This technique consists of the application of a topic, intravenous or oral photosensitizer that tend to concentrate preferentially in the injured tissue and subsequent irradiation with light of a specific wave length that, in the presence of molecular oxygen unchains a photochemical reaction, inducing the release of free radicals and resulting into the death of these cells among other local effects.…”