Impact of treatment response metrics on photodynamic therapy planning and outcomes in a three-dimensional model of ovarian cancer

Abstract

Abstract. Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching and viability, suggesting that it was a better reporter of PDT efficacy than total volume, which did not correlate with either metric. Based on these findings, live volume and viability are used to probe the susceptibilities of tumor populations to a range of PDT dose parameters administered using 0.25, 1, and 10 μM benzoporphyrin derivative (BPD). PDT with 0.25 μM BPD produces the most significant reduction in live volume and viability and mediates a substantial shift toward small nodules. Increasingly sophisticated bioengineered models may complement current treatment planning approaches and provide unique opportunities to critically evaluate key parameters including metrics of therapeutic response.

ECM Composition and Rheology Regulate Growth, Motility, and Response to Photodynamic Therapy in 3D Models of Pancreatic Ductal Adenocarcinoma

“…For treatments of 3D cell cultures, adaptation of an imaging-based methodology previously described was used (23,24). Briefly, this approach consists of image segmentation and quantitative analysis of fluorescence signal from vital dyes calcein AM (ThermoFisher Scientific Molecular Probes; Waltham, MA) and ethidium bromide (Fisher BioReagents; Pittsburgh, PA).…”

Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy

“…A number of studies in the literature have investigated the effect of PDT on ovarian and pancreatic cancer in a variety of models including cell lines [61], 3D cell culture [62][63][64], transplanted mice [65,66] and Phase I/II human trials [67,68]. A benzoporphyrin derivative (BPD) at 0.25 μM was able to reduce cell viability and volume in the human ovarian carcinoma cell line OVCAR5 and penetrate well through OVCAR5 3D cell culture [62,63].…”

“…A benzoporphyrin derivative (BPD) at 0.25 μM was able to reduce cell viability and volume in the human ovarian carcinoma cell line OVCAR5 and penetrate well through OVCAR5 3D cell culture [62,63]. In another study in which OVCAR5 cells were grown in a culture film a fibre optic delivery system was used where the PS (pheophorbide) and oxygen gas was delivered separately [64].…”

Photodynamic therapy as an effective therapeutic approach in MAME models of inflammatory breast cancer

“…In contrast, 3D models predict resistance to chemo- and radiation therapies [27–29]. Hasan and colleagues have adapted ovarian and pancreatic cancer cells to 3D models to evaluate PDT in photokilling these resistant cancer cells [30–32]. The 3D MAME culture model developed in our laboratory mimics in vivo architecture and allows studies of cell–cell interactions over time.…”