In order to investigate the interaction between the triplet state T1 and ground state oxygen 3O2 during pulsed
excitation photodynamic therapy (PDT), we measured the phosphorescence and singlet oxygen 1O2 fluorescence time-resolved
waveform. The phosphorescence time-resolved waveform from clinical photosensitizers has not been
obtained because this signal was buried in the photosensitizer fluorescence. We constructed the experimental setup
with a spectral and temporal filter to select the phosphorescence signals from the Photofrin(II)(R) and Talaporfin sodium
solution. The lifetimes and spectrums of the measured luminescence coincided with the phosphorescence
characteristics, respectively. We obtained the phosphorescence time-resolved waveforms from the clinical
photosensitizer solutions successfully. The 1O2 fluorescence time-resolved waveforms from these photosensitizers
were measured with an IR-PMT with a photon counter. The fluorescence time-resolved waveforms of each
photosensitizer were also obtained by the authors. We could consequently describe sequential generation of three
time-resolved waveforms throughout the photosensitive reaction in the clinical photosensitizers. We think we may
evaluate the photoseisitizer characteristics by these waveforms.
Photodynamic therapy (PDT) is promising modality for cancer. Prostate cancer is the most common cancer in USA. We proposed transurethral prostate cancer treatment using the pulse-intensity-domain depth-controlled PDT to preserve urethra wall. We have found that photocytotoxicity has been suppressed under high-intensity pulsed excitation with the second generation photosensitizers. We aim to apply this effect to form intact portion on the surface of the irradiated field. Irradiation condition dependence of photocytotoxicity of rat prostate cancer cell line R3327-AT-1 was investigated with two clinical photosensitizers, Porfimer sodium and Talaporfin sodium. A pulsed laser was irradiated with the power energy density ranging from 1.25 to 10 mJ/cm2. Near-infrared luminescence from singlet oxygen in the solution of those two photosensitizers was measured transiently. We performed PDT against a rat subcutaneous prostate tumor mode with Talaporfin sodium (2mg/kg) injected intravenously 1 h prior to the irradiation. The laser was irradiated with the power energy density 2.5 or 10 mW/cm2, with the total fluence of 50 J/cm2. Photocytotoxicity in vitro and the singlet oxygen generation were both suppressed with the 10mJ/cm2 irradiation with Talaporfin sodium, while these with Porfimer sodium were kept relatively constant. The surface of the irradiated field of 1mm in thickness remained intact, while the tumor damaged layer of 1.3 mm in thickness was obtained in the case of 10mJ/cm2 irradiation. We think Talaporfin sodium has high sensitivity to the pulse energy density, which might be useful to realize urethra preserved PDT for prostate cancer.
In order to attain complete seal of catheter sheath hole just after catheter intervention, we applied laser welding technique. We employed combination of diode laser (wavelength: 810nm) irradiation and indocyanine green stain to enhance heat generation on the stained surface. We studied laser sealing of catheter sheath hole on an ex vivo vascular model using porcine carotid artery.
We successfully demonstrated the sheath hole closure in this welding in the model with 1.8W, 8s diode laser irradiation. In this case, we estimated 78 °C of the maximum temperature at welding surface by thermal conduction calculation. Collagen fiber melting was found in welding region.
To know vascular wall at the fiber tip to perform laser welding in blind procedure, we constructed fiber-optic backscattering light measurement system. We used green He-Ne laser light (543nm) to distinguish hemoglobin concentration in the tissue. We obtained tissue discrimination at fiber tip in blind procedure. We think our particular laser welding in combination with novel tissue discrimination technique at the fiber tip may attain the catheter sheath hole closure with sufficient mechanical strength in blind procedure.
Photodynamic therapy against murine macrophage like cells with the second-generation hydrophilic photosensitizer ME2906 (mono-L-aspartyl chlorin e6:NPe6) was performed in vitro to study therapeutic effect distribution formation along depth with high-intensity pulsed irradiation. The photocytotoxicity of macrophage like cell with ME2906 under various fluence rates was measured. We found photocytotoxicity suppression from 64% to 16% in the cell lethality ranging the fluence rate of a pulsed laser from 20 to 400mW/cm2 (corresponding pulse peak power: from 0.07 to 1.4 MW/cm2). The cell lethality of about 80 % was obtained with continues wave laser irradiation under the fluence of 10 J/cm2. Photobleaching and oxygen consumption of the photosensitizer solution, were measured to know photoreaction of the photosensitizer solution under the high fluence rate pulsed irradiation. Type-II photochemical reaction suppression was indicated with the high fluence rate pulsed irradiation. The transient absorption of the photosensitizer solution during pulse irradiation was measured by the pump-and-probe technique with pulse peak power density up to 1.2 MW/cm2 to investigate absorption saturation. In the case of the pump beam peak power of 1.2MW/cm2, the transmittance of the probe beam increased approximately 7% from that of without the pump beam, so that huge absorption saturation did not occur in this case. We think the main cause of the photocytotoxicity suppression in this study may not to be attributed to the absorption saturation. This photocytotoxicity suppression induced by the high-intensity irradiation may be available to control treatment depth of PDT to preserve healthy internal wall of a hollow organ.
Photodynamic therapy (PDT) mechanism with high-intensity pulsed laser excitation has not been well understood. We think complete understanding of this unknown effect in PDT leads perfect treated depth control at various lesions. To realize the depth controlled PDT for atheromatous plaque therapy with a fibrous cap intact and surrounding damage free, we studied PDT against murine macrophage-like cells in vitro with the second-generation chlorin photosensitizer manufactured by Photochemical Co. Ltd. (Okayama Japan). The relation between the excitation conditions (pulse energy density and repetition rate) and PDT photocytotoxicity was examined in vitro. The XeCl excimer laser pumped dye laser (wavelength: 669±3 nm, pulse duration: 7ns in FWHM) was used with the pulse energy density from 1.2 to 9.5 mJ/cm2, and the pulse repetition rate from 5 to 80 Hz. Under higher pulse energy density condition, no significant PDT photocytotoxicity was obtained. We examined the photobleaching of the protein containing photosensitizer medium solution, which is considered to correlates with the generation of singlet oxygen. Under higher pulse energy condition, the photobleaching efficiency decrease was observed and the measured PDT effect decrease in terms of laser pulse energy density could be explained by the photobleaching. We measured the oxygen partial pressure in photosensitizer medium solution immediately after the laser exposure. The decrease of oxygen partial pressure, i.e., the amount of the oxygen consumption during the laser exposure was observed 46 mmHg under the excitation condition of the pulse energy density of 9.5 mJ/cm2, the total fluence of 5 J/cm2, the repetition rate of 80Hz, and correlated with the bleaching efficiency 87% under the same condition. We calculated cell death distribution in depth direction based on measured photocytotoxicity under various pulse energy densities. The possibility of depth controlled PDT for safety atheromatous plaque therapy was suggested by the PDT effect alteration depending on pulse energy density.
To develop the catheter-based laser vascular welding device against aortic dissection, we studied fundamental characteristics of the laser vascular welding for aorta dissection model in vitro with the scattering light monitoring to obtain welding proceedings. We employed the laser vascular welding by means of the combination of the diode laser irradiation and indocyanine green (ICG) stain to the dissected vessel surface in a swine aortic dissection model to obtain localized heat generation on the surface. The forward and backward scattering lights of the diode laser from the welding portion were measured during the laser irradiation. The breaking stresses of the welded aortic pieces were measured. The breaking stress of 170gf/cm2 obtained with the 425W/cm2, 2.4s irradiation may be strong enough to the successful therapy for aortic dissection regarding to the dissecting force caused by blood flow. By analyzing forward and backward scattering lights, we could observe the occurrence of water evaporation in the welding portion, the bleaching of the ICG and the carbonization of the welding portion. Then we could monitor the proceedings of the welding process. The temperature estimation of the welding portion and the microscopic observation revealed that the mechanism of our welding may be basically elastic fiber entwining. We think our vascular welding with the scattering light monitoring of the welding process has the potential to apply catheter-based therapy for aortic dissection.
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