In vivo anti-tumor activity of photodynamic therapy with intravenous administration of acridine orange, followed by illumination with high-power flash wave light in a mouse osteosarcoma model
Abstract:Abstract. In a recent study, we demonstrated that a high-power flash wave light (FWL) from a xenon lamp exerted a stronger cytocidal effect against a mouse osteosarcoma cell line than continuous wave light (CWL) in photodynamic therapy with acridine orange (AO-PDT). Based on our in vitro results, we investigated the in vivo anti-tumor activity of AO-PDT using flash wave light from a xenon lamp in a mouse osteosarcoma model. Mouse osteosarcoma cells (LM8) were injected into the subcutaneous tissue of the back o… Show more
“…Acridine orange and other nuclear contrast agents such as acriflavine and proflavine, have been used as in vivo nuclear contrast agents for microscopy. [40][41][42][43][44] The use of nuclear contrast agents in vivo for neuropathologic assessment may be of importance because nuclear assessment is critical for the diagnosis of many neurologic tumors. Acridine orange has also been recently demonstrated as a potential agent for neuro-oncologic photodynamic therapy.…”
Background: Microscopic delineation and clearance of tumor cells at neurosurgical excision margins potentially reduce tumor recurrence and increase patient survival. Probe-based in vivo fluorescence microscopy technologies are promising for neurosurgical in vivo microscopy.
Objective:We sought to demonstrate a flexible fiberoptic epifluorescence microscope capable of enhanced architectural and cytological imaging for in vivo microscopy during neurosurgical procedures.Methods: Eighteen specimens were procured from neurosurgical procedures. These specimens were stained with acridine orange and imaged with a 3D-printed epifluorescent microscope that incorporates a flexible fiberoptic probe. Still images and video sequence frames were processed using frame alignment, signal projection, and pseudo-coloring, resulting in resolution enhancement and an increased field of view.Results: Images produced displayed good nuclear contrast and architectural detail. Grade 1 meningiomas demonstrated 3D chords and whorls. Low-grade meningothelial nuclei showed streaming and displayed regularity in size, shape, and distribution. Oligodendrogliomas showed regular round nuclei and a variably staining background. Glioblastomas showed high degrees of nuclear pleomorphism and disarray. Mitoses, vascular proliferation, and necrosis were evident.
Conclusions:We demonstrate the utility of a 3D-printed, flexible probe microscope for highresolution microscopic imaging with increased architectural detail. Enhanced in vivo imaging using this device may improve our ability to detect and decrease microscopic tumor burden at excision margins during neurosurgical procedures.
“…Acridine orange and other nuclear contrast agents such as acriflavine and proflavine, have been used as in vivo nuclear contrast agents for microscopy. [40][41][42][43][44] The use of nuclear contrast agents in vivo for neuropathologic assessment may be of importance because nuclear assessment is critical for the diagnosis of many neurologic tumors. Acridine orange has also been recently demonstrated as a potential agent for neuro-oncologic photodynamic therapy.…”
Background: Microscopic delineation and clearance of tumor cells at neurosurgical excision margins potentially reduce tumor recurrence and increase patient survival. Probe-based in vivo fluorescence microscopy technologies are promising for neurosurgical in vivo microscopy.
Objective:We sought to demonstrate a flexible fiberoptic epifluorescence microscope capable of enhanced architectural and cytological imaging for in vivo microscopy during neurosurgical procedures.Methods: Eighteen specimens were procured from neurosurgical procedures. These specimens were stained with acridine orange and imaged with a 3D-printed epifluorescent microscope that incorporates a flexible fiberoptic probe. Still images and video sequence frames were processed using frame alignment, signal projection, and pseudo-coloring, resulting in resolution enhancement and an increased field of view.Results: Images produced displayed good nuclear contrast and architectural detail. Grade 1 meningiomas demonstrated 3D chords and whorls. Low-grade meningothelial nuclei showed streaming and displayed regularity in size, shape, and distribution. Oligodendrogliomas showed regular round nuclei and a variably staining background. Glioblastomas showed high degrees of nuclear pleomorphism and disarray. Mitoses, vascular proliferation, and necrosis were evident.
Conclusions:We demonstrate the utility of a 3D-printed, flexible probe microscope for highresolution microscopic imaging with increased architectural detail. Enhanced in vivo imaging using this device may improve our ability to detect and decrease microscopic tumor burden at excision margins during neurosurgical procedures.
“…When exposed to low doses of radiograph radiation, AO also increases the production of reactive radicals. 4 Kusuzaki et al 1 and Satonaka et al 3 , 7 developed photodynamic and radiodynamic therapies with AO (AO-PDT and AO-RDT) using in vitro and in vivo studies. In addition, other studies observed excellent clinical outcomes in patients with bone and soft-tissue sarcomas who received AO-PDT and AO-RDT.…”
Aims Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):685–692.
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