Towards Bimodal Optical Monitoring of Photodynamic Therapy with Targeted Nanoconstructs: A Phantom Study

Increase of the efficiency of photodynamic therapy (PDT) requires the development of advanced protocols employing both novel photosensitizer (PS) carriers and aids for online monitoring. Nanoconstructs may be comprised of a photosensitizer, chemotherapy drugs, or inhibitors of molecular pathways that support cancer growth. In this paper, we analyze the efficiency of a bimodal approach involving fluorescence and optoacoustic imaging in monitoring drug distribution and photobleaching. The study evaluates typical sensitivities of these techniques to the presence of the two key moieties of a nanoconstruct: benzoporphyrin derivatives (BPD) serving as a PS, and IRDye800 acting as a contrast agent. Both imaging modalities employ dual-wavelength probing at the wavelengths corresponding to absorption peaks of BPD and IRDye800, which enables their separate detection. In an experiment on a tissue-mimicking phantom with inclusions containing separate BPD and IRDye800 solutions, fluorescence imaging demonstrated higher contrast as compared to optoacoustic imaging for both components, though strong light scattering in the surrounding media restricted accurate localization of the markers. It was also sensitive to photobleaching, which is a measure of PDT efficiency. Optoacoustic imaging demonstrated sufficient sensitivity to both components, though less than that of fluorescence imaging, however, it enabled depth-resolved detection of an absorber and estimation of its relative content. Employment of the bimodal approach in monitoring of PS photobleaching adds to its potential in intraprocedural PDT monitoring.