CC BY
18B-I-12
Complementary approach to monitoring of photodynamic therapy with target nanoconstructs by fluorescence and optoacoustic imaging
I. Turchin1, M. Kirillin1, D. Kurakina1, V. Perekatova1, A. Orlova1, E. Sergeeva1, V. Plekhanov1, P. Subochev1, S. Mallidi2, T. Hasan2
institute of Applied Physics of the Russian Academy of Sciences, Radiophysical methods in medicine, Nizhny Novgorod, Russian Federation 2Massachusetts General Hospital- Harvard Medical School, Wellman Center for Photomedicine, Boston, USA
We proposed a new complementary approach to monitoring of photodynamic therapy (PDT) of glioblastoma with the use of targeted nanoconstructs containing a photosensitizer (PS) benzoporphyrin derivative (BPD) and IRDye800 dye, antibodies for efficient accumulation of the drug in a tumor, and a chemotherapeutic agent for combined effect on tumor cells. Monitoring of PDT was based on the simultaneous fluorescent and optoacoustic (OA) imaging. The possibilities of a complementary approach were demonstrated in numerical simulations, phantom and in vivo studies.
Fluorescence images were simulated by two-step Monte Carlo technique: at first step the distributed fluorescence source is calculated as excitation radiation absorption map; at the second step fluorescence emission is simulated. Monte Carlo simulations combined for OA imaging with k-wave modeling allowed to study the feasibility of the complementary approach.
The optical phantom was designed as a mixture of agar, water, 20% Lipofundin and black ink. The concentrations of the phantom components were chosen to mimic optical properties of mice brain tissue at the excitation and detection wavelengths of both dyes. The liquid phantom was poured into the special cuvette with three transparent plastic tubes filled with IRDye800, BPD and DMSO.
The custom-made fluorescence imaging setup employed in the study included a CCD camera, a filter wheel, and an illumination system adapted for nanoconstruct components (both IRDye800 and BPD dyes). The OA imaging setup employed the concept of dark-field acoustic resolution photoacoustic microscopy, where the scanning OA head is represented by a conical fiber-optic illumination system combined with a spherically focused acoustic detector made of a polyvinylidene difluoride piezo film with a 25 p,m thickness. OA experiments were performed at the wavelengths of 690 nm and 785 nm corresponding to the maxima of the optical absorption spectra of BPD and IRDye800 markers.
Fluorescence imaging demonstrated higher contrast as compared to optoacoustic imaging for both components, however, strong light scattering in the surrounding media prevented accurate location of the markers. OA imaging demonstrated the sensitivity to both components enabling depth-resolved detection. Complementary information from fluorescence and OA imaging was shown to be useful in characterizing the drug containing volume. Perspectives of the developed approach in monitoring of a PDT procedure was studied in course of the BPD photobleaching. Fluorescent imaging is sensitive to photobleaching which is a measure of PDT efficiency, and it does not require direct contact with the tissue. Employment of the bimodal approach in monitoring of PS photobleaching indicated its high potential in intraprocedural PDT monitoring.
The work was carried out as part of the RFBR project 17-54-33043 onko-a.
