CC BY
0Recent advances in dual-wavelength fluorescence imaging with chlorin-based photosensitizers
A. Khilov1*, D. Kurakina1, A. Malygina2, E. Sergeeva1, A. Mironycheva12, V. Perekatova1, I. Shlivko2, S. Gamayunov13, I. Turchin1, M. Kirillin1
1-A.V. Gaponov-Grekhov Institute of Applied Physics of the Russian Academy of Sciences, 46 Ul'yanov Street,
Nizhny Novgorod, 603950, Russia
2- Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Sq., Nizhny Novgorod, 603005, Russia
3- Nizhny Novgorod Regional Oncological Hospital, Delovaya 11/1, Nizhny Novgorod, 603126, Russia
* alhil@inbox.ru
Photodynamic therapy (PDT) is a modern rapidly developing treatment technique based on photoactivation of a photosensitizer (PS), which is accumulated primarily in abnormal cells after its administration prior to the procedure. Photodynamic reaction is launched by consecutive therapeutic light exposure, which produces singlet oxygen inducing abnormal cells death. This treatment technique has shown its efficiency against a number of tumor and non-tumor pathologies [1]. Moreover, PDT efficiency can be enhanced by its repetition or combination with other treatment modalities or corrections in PDT regimen, which includes variations of delivered light dose and PS concentration, thus implementing the trending principles of personalized medicine. A number of imaging techniques are reported for non-invasive monitoring of PDT, while the most promising tools for real-time PDT control are optical imaging methods.
Since most of PSs possess fluorescence properties, it is reasonable to merge therapy and fluorescence diagnostics, thus implementing theranostics principles. Fluorescence imaging (FI) allows for normal/pathology differentiation and imaging-guided surgery [2] as well as for the assessment of PDT efficiency upon decrease in PS fluorescence, known as PS photobleaching [3].
The employment of PS with two or more peaks in absorption spectrum (chlorin e6, PPIX and others) allows for the choice of PDT regimen [4] and, consequently, of therapeutic impact depth. Dual-wavelength fluorophore excitation also allows for the estimation of fluorophore localization based on ratiometric approach [5,6]. Ratiometric approach requires a priori knowledge of optical properties of surrounding tissues, thus, dual-wavelength FI combined with diffuse reflectance spectroscopy, which allows for non-invasive estimation of optical properties based on registered diffuse reflectance spectrum, may further enhance the efficiency of reported technique.
We present the results of in vivo dual-wavelength FI of actinic keratosis and basal cell carcinoma PDT procedures with chlorin-based PS performed in clinical environment. It is shown that dual-wavelength ratiometric FI not only provides with the estimations of therapeutic impact depth, but also reveals prognostic factors for long-term prognosis of target tissue response to PDT.
The study is supported by Russian Science Foundation (project #24-15-00175).
[1] J.P. Celli, B.Q. Spring, I. Rizvi, C.L. Evans, K.S. Samkoe, S. Verma, B.W. Pogue, T. Hasan, Imaging and photodynamic therapy: mechanisms, monitoring, and optimization, Chemical reviews 110, 2795-2838 (2010).
[2] J. He, L. Yang, W. Yi, W. Fan, Y. Wen, X. Miao, L. Xiong, Combination of fluorescence-guided surgery with photodynamic therapy for the treatment of cancer, Molecular imaging 16, 1536012117722911 (2017).
[3] A. Johansson, F. Faber, G. Kniebuhler, H. Stepp, R. Sroka, R. Egensperger, W. Beyer, F.W. Kreth, Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis, Lasers in surgery and medicine 45, 225-234 (2013).
[4] M. Kirillin, D. Kurakina, A. Khilov, A. Orlova, M. Shakhova, N. Orlinskaya, E. Sergeeva, Red and blue light in antitumor photodynamic therapy with chlorin-based photosensitizers: a comparative animal study assisted by optical imaging modalities, Biomedical Optics Express 12, 872-892 (2021).
[5] A.V. Khilov, E.A. Sergeeva, D. Kurakina, I.V. Turchin, M.Y. Kirillin, Analytical model of fluorescence intensity for the estimation of fluorophore localisation in biotissue with dual-wavelength fluorescence imaging, Quantum Electronics 51, 95 (2021).
[6] M. Kirillin, A. Khilov, D. Kurakina, A. Orlova, V. Perekatova, V. Shishkova, A. Malygina, A. Mironycheva, I. Shlivko, S. Gamayunov, Dual-Wavelength Fluorescence Monitoring of Photodynamic Therapy: From Analytical Models to Clinical Studies, Cancers 13, 5807 (2021).
