Tumor fluorescence and oxygenation monitoring during photodynamic therapy with chlorin e6 photosensitizer.

BACKGROUND: The study is aimed at developing a method for monitoring photodynamic therapy (PDT) of a tumor using chlorin-type photosensitizers (PSs). Lack of monitoring of chlorin e6 (Cе6) photobleaching, hemoglobin oxygenation and blood flow during light exposure can limit the PDT effectiveness. MATERIALS AND METHODS: Phototheranostics includes spectral-fluorescence diagnostics of Ce6 distribution in the NIR range and PDT with simultaneous assessment of hemoglobin oxygenation and tumor blood flow. Fluorescence diagnostics and PDT were performed using the single laser λexc=660 ± 5 nm. RESULTS: Combined spectroscopic PDT monitoring method allowed simultaneous estimation of Ce6 photobleaching, hemoglobin oxygenation and tumor vascular thrombosis during PDT without interrupting the therapeutic light exposure. CONCLUSION: The developed method of tumor phototheranostics using chlorin-type PSs may make it possible to personalize the duration of therapeutic light exposure during PDT.

Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age.

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22-49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients.

Phototheranostics of Cervical Neoplasms with Chlorin e6 Photosensitizer.

(1) Purpose: Improving the treatment effectiveness of intraepithelial neoplasia of the cervix associated with human papillomavirus infection, based on the application of the method of photodynamic therapy with simultaneous laser excitation of fluorescence to clarify the boundaries of cervical neoplasms. (2) Methods: Examination and treatment of 52 patients aged 22 to 53 years with morphologically and cytologically confirmed mild to severe intraepithelial cervix neoplasia, preinvasive, micro-invasive, and squamous cell cervix carcinoma. All patients were carriers of human papillomavirus infection. The patients underwent photodynamic therapy with simultaneous laser excitation of fluorescence. The combined use of video and spectral fluorescence diagnostics for cervical neoplasms made it possible to control the photodynamic therapy process at all stages of the procedure. Evaluation of the photodynamic therapy of intraepithelial cervical neoplasms was carried out with colposcopic examination, cytological conclusion, and morphological verification of the biopsy material after the photodynamic therapy course. The success of human papillomavirus therapy was assessed based on the results of the polymerase chain reaction. (3) Results. The possibility of simultaneous spectral fluorescence diagnostics and photodynamic therapy using a laser source with a wavelength of 660 nm has been established, making it possible to assess the fluorescence index in real-time and control the photobleaching of photosensitizers in the irradiated area. The treatment of all 52 patients was successful after the first photodynamic therapy procedure. According to the PCR test of the discharge from the cervical canal, the previously identified HPV types were not observed in 48 patients. Previously identified HPV types were absent after repeated PDT in four patients (CIN III (n = 2), CIS (n = 2)). In 80.8% of patients, regression of the lesion was noted. (4) Conclusions. The high efficiency of photodynamic therapy with intravenous photosensitizer administration of chlorin e6 has been demonstrated both in relation to eradication therapy of human papillomavirus and in relation to the treatment of intraepithelial lesions of the cervix.