Al treatment outcomes, CW lasers appear to have gained more traction as clinically used light sources to date. The type of light source used (CW or pulsed), the concentration of the PS at the treatment site also play an important role in determining the depth of necrosis induced by PDT. [35]. A lesion with a very high PS concentration may prevent light from penetrating to the deeper regions of the tumor due to a phenomenon known as PS self-shielding, in which saturated Doravirine site concentrations of the PS absorb a major portion of the incident light in the superficial layers. According to Pogue et al, a high intensity pulsed beam might have advantages over CW due to the transient change in absorption of the PS that allows the latter parts of the laser pulse to pass through the surface layers with less attenuation. In simple terms, the photobleaching or destruction of PS in the top layer will allow subsequent light to not be attenuated, and reach deeper tissues creating a “layer-by-layer” PDT effect [30]. Clinically, achieving high concentrations of PS may require DM-3189 web either a localized intra-lesional PS injection or to limit PDT to nearly transparent tissues in which the PS absorption is much higher than that of tissue. A study by Rizvi et al also showed that high concentrations of PS may not translate to effective PDT therapy [36]. These observations point to the importance of “right” amount of PS and “right” light irradiance to obtain an effective treatment outcome. Another strategy utilized by our group and others to enhance PDT efficacy is to combine two or more PSs [37]. For example, Cincotta et al demonstrated that large RIF tumors were more effectively treated with ahttp://www.thno.orgPulsed or fractionated PDT regimes for achieving enhanced necrotic depthContinuous wave (CW) lasers or light sources have traditionally been used for PDT. However, as the availability of pulsed lasers increased, several groups, including ours, have compared the effectiveness of pulsed lasers and CW irradiation for PDT since the late 1980s. Pulsed laser illumination was thought to enhance PDT efficacy primarily due to hypothesis that the downtime between light irradiation will: 1. Allow the tissue to re-oxygenate, making subsequent irradiations effective and 2. Allow re-accumulation of photosensitizer at the lesion [23]. While a few studies have shown that the necrotic depth induced by CW lasers is similar to thaFt seen with pulsed lasers, other studies have shown significant enhFancement in the necrotic depth resulting from pulsed irradiation [24-29]. For example, a study by the Bown group showed comparable outcomes between phthalocyanine (ALSPc) based PDT using an argon ion pumped CW dye laser with a copper vapour pumped dye pulsed laser (10KHz repetition rate) [28]. The same study also demonstrated that a low repetition rate with a high pulse energy source such as the flashlamp of a 5 Hz pumped dye laser is not an efficient irradiation source for PDT. Our group also demonstrated no statistically significant difference in the depth of necrosis 48 hrs post PDT with CW or the pulsed irradiation with the same average incidentTheranostics 2016, Vol. 6, Issuecombination of Benzoporphyrin Derivative (BPD)-PDT and EtNBs-PDT compared to PDT with individual PS alone. This combination of PSs was chosen because each PS targets different compartments of the tumors (oxygenated vs hypoxic, vascular vs cellular) allowing for a better overall therapeutic outcome [38]. Another str.Al treatment outcomes, CW lasers appear to have gained more traction as clinically used light sources to date. The type of light source used (CW or pulsed), the concentration of the PS at the treatment site also play an important role in determining the depth of necrosis induced by PDT. [35]. A lesion with a very high PS concentration may prevent light from penetrating to the deeper regions of the tumor due to a phenomenon known as PS self-shielding, in which saturated concentrations of the PS absorb a major portion of the incident light in the superficial layers. According to Pogue et al, a high intensity pulsed beam might have advantages over CW due to the transient change in absorption of the PS that allows the latter parts of the laser pulse to pass through the surface layers with less attenuation. In simple terms, the photobleaching or destruction of PS in the top layer will allow subsequent light to not be attenuated, and reach deeper tissues creating a “layer-by-layer” PDT effect [30]. Clinically, achieving high concentrations of PS may require either a localized intra-lesional PS injection or to limit PDT to nearly transparent tissues in which the PS absorption is much higher than that of tissue. A study by Rizvi et al also showed that high concentrations of PS may not translate to effective PDT therapy [36]. These observations point to the importance of “right” amount of PS and “right” light irradiance to obtain an effective treatment outcome. Another strategy utilized by our group and others to enhance PDT efficacy is to combine two or more PSs [37]. For example, Cincotta et al demonstrated that large RIF tumors were more effectively treated with ahttp://www.thno.orgPulsed or fractionated PDT regimes for achieving enhanced necrotic depthContinuous wave (CW) lasers or light sources have traditionally been used for PDT. However, as the availability of pulsed lasers increased, several groups, including ours, have compared the effectiveness of pulsed lasers and CW irradiation for PDT since the late 1980s. Pulsed laser illumination was thought to enhance PDT efficacy primarily due to hypothesis that the downtime between light irradiation will: 1. Allow the tissue to re-oxygenate, making subsequent irradiations effective and 2. Allow re-accumulation of photosensitizer at the lesion [23]. While a few studies have shown that the necrotic depth induced by CW lasers is similar to thaFt seen with pulsed lasers, other studies have shown significant enhFancement in the necrotic depth resulting from pulsed irradiation [24-29]. For example, a study by the Bown group showed comparable outcomes between phthalocyanine (ALSPc) based PDT using an argon ion pumped CW dye laser with a copper vapour pumped dye pulsed laser (10KHz repetition rate) [28]. The same study also demonstrated that a low repetition rate with a high pulse energy source such as the flashlamp of a 5 Hz pumped dye laser is not an efficient irradiation source for PDT. Our group also demonstrated no statistically significant difference in the depth of necrosis 48 hrs post PDT with CW or the pulsed irradiation with the same average incidentTheranostics 2016, Vol. 6, Issuecombination of Benzoporphyrin Derivative (BPD)-PDT and EtNBs-PDT compared to PDT with individual PS alone. This combination of PSs was chosen because each PS targets different compartments of the tumors (oxygenated vs hypoxic, vascular vs cellular) allowing for a better overall therapeutic outcome [38]. Another str.