Photodynamic Therapy as a New Treatment Method in Veterinary Oncology

Nemtseva Yuliya Sergeevna Postgraduate at the Department of Veterinary Medicine of the Institute of Veterinary and Sanitary Expertise, Biological and Food Security, Moscow State University of Food Production 125080, Russia, g. Moscow, shosse Volokolamskoe, 11, kab. 236 jul555lia@yandex.ru

Relevance

The basis of tumor growth is the limitless, uncontrolled multiplication of cells by the body, which leads to dysfunction, tissue destruction, and, eventually, death.

The development of mammary gland neoplasms in animals is a serious problem in modern veterinary medicine and veterinary oncology. Recent statistics have convincingly demonstrated an increase in the incidence of carnivorous animals, so it is necessary to develop and implement the latest effective methods for diagnosing and treating malignant neoplasms. According to literature sources from both domestic and foreign scientists, neoplasms in animals account for 2% to 18% of the total number of diseases ^[3].

Breast tumors are divided into benign and malignant tumors. Benign neoplasms include fibroadenoma, adenoma, and mixed-type benign tumors. Of the malignant tumors, carcinoma is the most common.

The main diagnostic methods, taking into account the possibility of metastasis of breast tumors, include primary examination of the tumor, X-ray examination of the thoracic cavity, and ultrasound diagnostics. Morphological verification of the diagnosis is carried out by histological examination of the surgical material. Aspiration puncture biopsy with cytological examination of the material is also used. Additional methods include scintigraphy to determine metastatic bone lesions, computed tomography (CT) for suspected generalized breast tumors, and magnetic resonance imaging (MRI) to determine the exact location of the tumor using a three-dimensional image.

The relevance of the topic is due to the fact that breast tumors are a common disease in carnivorous animals. The search for new effective means and methods necessary for diagnosing, treating, and preventing malignant neoplasms is an urgent problem in modern veterinary medicine ^[4].

The main part

There are several theories and hypotheses of oncogenesis (chemical, chromosomal, viral, hereditary, and others). Still, none of them is considered a single one recognized by all, as they only reflect different aspects of the same process: damage to the cell genome. Any living cell contains proto-oncogenes in the DNA structure—these are sections of the cell genome that, under certain conditions, transform into an active form—oncogenes. The latter, in turn, causes malignant cell degeneration, which gives rise to tumor growth. The main factors of carcinogenesis can be of both endogenous and exogenous origin ^[3]

A static study has shown that the majority of cases of breast tumors occur in cats. However, mongrels lead when analyzing breed predisposition to breast tumors among cats and dogs. There is also a predisposition in British cat breeds and among dogs in Yorkshire and Toy Terriers. The analysis of the age index revealed the highest percentage of breast tumors in cats in the 11—to 15-year-old age group and in dogs in the 8—to 10-year-old age group.

The main feature of feline breast cancer is its high aggressiveness and the speed of the process. Breast cancer is almost 3 times less common in dogs than cats ^[6].

More than 80% of cat breast tumors are carcinomas, and the rest are mainly fibroadenomas. Lobular hyperplasia (palpable formations in one or more glands) and fibroepithelial hyperplasia of the mammary gland (hypertrophy of the mammary gland in cats) are also found, and they are believed to be associated with hormonal stimulation of glandular tissue.

Treatment of neoplasms should always be carried out comprehensively. When drawing up a treatment plan, it is necessary to take into account the high aggressiveness of malignant neoplasms, the stage of the process, possible aggravating factors (age, serious condition, etc.), which dictates the need to use various methods of combined and complex therapy ^[7]

Photodynamic therapy is used when surgical operation is impossible due to the prevalence of the tumor process or severe concomitant diseases. Therefore, if an animal has a malignant tumor that cannot be surgically removed, photodynamic therapy can be used to treat such tumors.

Photodynamic therapy is a new method of treating oncological, specific skin, and infectious diseases. It involves using photosensitive substances—photosensitizers of visible light of a certain wavelength.

Photodynamic therapy includes four stages:

1. intravenous photosensitizer injection.

2. accumulation of the drug in the tissues affected by the cancer.

3. the stage of irradiation of the tumor with a laser. This stage's time depends on the tumor’s size, location, and shape.

4. the stage of the collapse of a cancerous tumor and the restoration of tissues that have undergone mutation ^[5].

The effectiveness of this method lies in the photodynamic damage of the cancer cell during the photochemical reaction. Photodynamic therapy is a treatment method based on two components. The first component is a drug that accumulates for a long time in a cancer cell, and the second component is light exposure. During photodynamic therapy, light is exposed with a specific wavelength corresponding to the absorption peak of the photosensitizer. At this point, a chemical reaction occurs, releasing singlet oxygen and oxygen free radicals, which have a toxic effect on cancer cells. The cells necrotize and are gradually replaced by connective tissue. During the procedure, small blood vessels that supplied cancer cells with blood die.

Photosensitizers are photosensitive substances capable of receiving and transmitting light energy. Special photosensitizers are injected into the patient’s body (intravenously, applicatively, or orally), and they selectively accumulate in cancer cells while practically not lingering in healthy cells.

Currently, all photosensitizers are divided into two generations. The first generation is hematoporphyrin, whose derivative is photogram (Russia). A derivative of the chloride series, photoditosine, is widely used among second-generation photosensitizers.

Photoditazine is a second-generation photosensitizer designed for fluorescence diagnostics and photodynamic therapy of malignant tumors. It is a drug of selective accumulation in malignant neoplasms. Upon subsequent irradiation with monochromatic light with a wavelength of 661–662 nm. The tumor focus has a photosensitizing effect, which consists of generating reactive oxygen species (singlet oxygen) and other free radical particles in the tumor tissue, leading to the development of structural, functional, and biochemical changes in tumor cells and their death. The high photocytotoxicity of Photoditazine is characteristic of various types of tumor cells. It is a highly informative diagnostic tool for spectrofluorescence research methods.

One of the most important features of the drug Photoditazine is the practical absence of dark cytotoxicity. The drug is rapidly eliminated from the body (within 24–28 hours), primarily from the skin and mucous membranes. It has a high tropicity (i.e., the ratio of drug concentrations in the tumor and normal tissue). During photodynamic therapy, these drug features exclude the damaging effect on healthy organs and tissues.

It has high photodynamic activity and high contrast (the concentration ratio in altered and normal tissues is 10:1, respectively), and 6% of the administered amount is observed in the body after a day ^[5].

To emit light energy, devices are used—"Garnet" and "LAMEDA"—which are irradiated with laser light of a strictly defined wavelength (depending on the photosensitizer used) and power.

The photodynamic therapy procedure is carried out as follows: the photosensitizer photoditosin is slowly injected intravenously through an infusion or drip at a dose of 0.8-1 mg/kg, diluted in NaCl 1 solution. Next, the animal is placed in a darkened room. Within a few hours, the photosensitizer accumulates in the tumor tissue, which can be monitored using fluorescence diagnostics. After three hours, after the accumulation of photosensitizer in the tumor, the tumor zone is irradiated with the capture of 1 cm of healthy tissue around the tumor with coherent laser radiation with a wavelength of 660 ± 2 nm in the red region of the spectrum, with a power of 1.5 watts. Laser radiation with an energy density of 300 J/cm2 is applied to the foci. After a photodynamic therapy session for 6–10 days, the tumor underwent necrosis and was rejected ^[5].

In veterinary medicine, photodynamic therapy has the following advantages:

1. It is used when surgical intervention is impossible due to severe concomitant diseases or the prevalence of the tumor process.;

2. In the preoperative period, it allows for the reduction of the volume of resection, increases radicalism in the operation, and improves treatment results.;

3. Photodynamic therapy can be used as an additional method of treatment and therapy after surgical removal of the tumor as, in many cases, microscopic foci of cancer remain after the resection of solid formations, which can lead to the development of recurrence or metastasis.;

4. The photosensitizer selectively accumulates in the tumor and almost does not linger in the normal tissues surrounding the tumor. Due to this, a cancerous tumor is damaged during photodynamic therapy during irradiation, and the surrounding tissues are not.;

5. The possibility of repetition of the treatment session if necessary;

6. Photodynamic therapy is a gentle, local, and inexpensive method of treating many types of malignant tumors (primary, recurrent, or metastatic) ^[6].

Photodynamic therapy can be combined with radiation or chemotherapy, as well as surgery, which can achieve significant results in the treatment of cancer.

However, photodynamic therapy also has several disadvantages:

1. Restrictions on access to light, that is, the part located directly under the skin, is amenable to treatment.

2. After photosensitizers, sensitivity to light remains for a while.

Conclusion

Malignant and benign breast tumors are one of the most common pathologies in small domestic animals, and malignant forms of tumors predominate in the overall structure of neoplasms. Cats account for the majority of cases of breast tumors.

Photodynamic therapy has great potential for treating tumors, including breast tumors. This method can be successfully used as an independent technique to treat malignant breast tumors, especially if other treatment methods are contraindicated. However, treating common tumors and metastases presents some difficulties. Therefore, it is necessary to study and implement this method in veterinary practice further to obtain better results from treating breast tumors in animals.