Abstract
Objective: The aim of this study was to demonstrate the clinical feasibility of intraoperative photodiagnosis (PD) of malignant brain tumor using talaporfin sodium (TPS), which is an agent used in photodynamic therapy (PDT) for cancers.Methods: Forty-seven patients diagnosed with malignant gliomas by preoperative imaging (42 patients with gliomas and 5 patients with other brain tumors) received an intravenous injection of TPS at 40 mg/m2 24 h before resection. During surgery, these patients were irradiated with diode laser light at 664 nm, and tumor fluorescence was observed. The fluorescence intensity was visually rated on a 3-point rating scale [strong fluorescence, weak fluorescence and no fluorescence]. TPS concentrations in 124 samples from 47 cases were measured by HPLC (High performance liquid chromatography).Results: The fluorescence intensity was confirmed to be weak in all patients with Grade II gliomas and strong in almost all patients with Grade III or IV gliomas, reflecting the histological grade of malignancy. In patients with non-glioma brain tumors except for 1 patient with a metastatic brain tumor, the fluorescence intensity was strong. The mean TPS concentration in tissues was 1.62 μg/g for strong fluorescence areas, 0.67 μg/g for weak fluorescence areas and 0.19 μg/g for no fluorescence areas.Conclusions: Establishment of an appropriate fluorescence observation system enabled fluorescence-guided resection of malignant brain tumors using TPS, and the fluorescence intensity of tumors correlated with the TPS concentrations in tissues. These results suggest that TPS is a useful photosensitizer for both intraoperative fluorescence diagnosis and photodynamic therapy.
Highlights
The use of photosensitizers (PSs) for malignant gliomas has been aimed mainly at tumor control by photodynamic therapy (PDT)
Talaporfin sodium (TPS: Laserphyrin R, Meiji Seika Pharma Co., Ltd., Tokyo, Japan) is a photosensitizer, a hydrophilic compound manufactured by coupling aspartic acid and chlorine, utilized in PDT, which was approved for use in Japan in 2003 as treatment for early-stage lung cancer, in combination with a diode laser (PD Laser R, Panasonic HealthCare Co., Ltd., Ehime, Japan) at a wavelength of 664 nm (Figures 1A,B)
This has enabled the period of necessary light shielding in a room with measurement of ≦ 500 lux to be reduced to 2 weeks for talaporfin sodium (TPS), whereas porfimer sodium requires patients to stay in a semi-dark (≦ 300 lux) room for 1 month after administration
Summary
The use of photosensitizers (PSs) for malignant gliomas has been aimed mainly at tumor control by photodynamic therapy (PDT). The main mechanism of PDT is based on the generation of cytotoxic singlet oxygen in tissues under aerobic conditions, Photodiagnosis for Glioma as a result of a photochemical reaction induced by the administration of a non-toxic PS in combination with the irradiation of an excitation laser specific to the PS. In 2000, Stummer et al established a methodology called fluorescence-guided resection (FGR) where tumors are resected using an intraoperative photodiagnosis (PD) of malignant gliomas with the fluorescence as a guide [8, 9]. No evidence for the usefulness of 5-ALA in PDT comparable to that in PD has been reported [13, 14]
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