Estimation of chlorin-based photosensitizer penetration depth prior to photodynamic therapy procedure with dual-wavelength fluorescence imaging

Abstract

Photodynamic therapy (PDT) is a modern treatment technique employed as an antitumor, antibacterial, or rejuvenation aid in superficial tissues. The use of fluorescent photosensitizers (PSs) implements the principles of theranostics when the applied medical agents serve both for diagnostic and treatment purposes. For efficient PDT performance it is important to evaluate the in-depth distribution of PSs in tissues prior to irradiation. Fluorescence imaging is a common technique to monitor the distribution of PSs in tissue. However, in-depth resolution is challenging. Chlorin-based PSs reveal two narrow fluorescence excitation peaks at 405 and 660 nm providing additional diagnostic opportunities. We demonstrate that the ratio of the fluorescence signals upon excitation at these wavelengths provides the evaluation of the PS penetration depth after topical application. The study is based on Monte Carlo simulations that are in agreement with phantom experiments. The effect of medium optical properties on the depth-dependent fluorescence signal ratio is analyzed.

Comparative analysis of single- and dual-wavelength photodynamic therapy regimes with chlorin-based photosensitizers: animal study

“…Note that the large standard deviations are determined by the differences in the absolute values, while the same trends are observed in all individual cases. In accordance with Monte Carlo simulations performed for the considered three-layered model using the previously developed methodology, 33 the values of R λ of ∼0.8 to 1.1 correspond to the typical penetration depth of 0.4 to 0.8 mm, which is in agreement with typical impact depths in a rabbit ear.…”

“…Monitoring of PS accumulation in the target area and its photobleaching in the course of the PDT procedure was performed by an FI device (IAP RAS, Russia) with probing wavelengths of 405 and 660 nm corresponding to the absorption bands of chlorin e6, and fluorescence detection in the range of 702 to 842 nm. 33,39 The device provides two-dimensional fluorescence images of the target area at both excitation wavelengths. This approach allows to indirectly estimate the PS penetration depth and the range of PDT action depths basing on the red-to-blue signal ratio dynamics R λ ¼ I f660 ∕I f405 , where I f660 and I f405 are the fluorescence intensities averaged over the region of interest upon excitation at wavelengths of 660 and 405 nm, respectively.…”

“…This approach allows to indirectly estimate the PS penetration depth and the range of PDT action depths basing on the red-to-blue signal ratio dynamics R λ ¼ I f660 ∕I f405 , where I f660 and I f405 are the fluorescence intensities averaged over the region of interest upon excitation at wavelengths of 660 and 405 nm, respectively. 32,33 FI was performed on the day of the PDT procedure only. The drop in the fluorescence signal, indicating PS photobleaching, was considered as an indicator of the procedure efficiency.…”

“…in turbid media followed by the statistical analysis of the collected data. A custom-developed MATLAB-based implementation 24,33 of Monte Carlo algorithm was employed to simulate the distribution of absorbed light dose in a rabbit ear for irradiation at 405 and 660 nm. Simulations were performed for a planar three-layered model of a rabbit ear with the thickness of 1 mm, where top and bottom layers correspond to the skin tissues and the intermediate layer corresponds to the cartilage.…”

“…The ratio of the fluorescence response values at these wavelengths yields the information about the penetration depth of PS upon topical administration, since prevailing response at blue-light excitation indicates accumulation in superficial layers, while prevailing response at red-light excitation indicates deeper PS penetration. 32,33 Optical coherence tomography (OCT) with angiographic modality provides complementary diagnostic opportunities in noninvasive immediate monitoring of PDT response such as visualization of structural and vascular changes caused by a PDT procedure. For instance, optical coherence angiography (OCA) was used to monitor treatment response following vasculartargeted PDT, 34,35 and a criterion of PDT success based on OCA images of tumor and peritumor areas acquired 24 h post treatment was suggested.…”