Predictive Dosimetry for Threshold Phototoxicity in Photodynamic Therapy on Normal Skin: Red Wavelengths Produce More Extensive Damage Than Blue at Equal Threshold Doses

Abstract

The goal of this investigation was to establish methodology to determine and prevent phototoxic responses of normal skin to photodynamic therapy (PDT). The drug used was a second-generation photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA). The dependence of skin phototoxicity on drug dose (0.5-2.0 mg/kg), fluence (1.2-390 J/cm2), and wavelength (690 nm and 458 nm) was studied in the New Zealand albino rabbit in the first 5 h after injection. Skin responses were recorded for 2 wk after irradiation. Noninvasive measurements of drug fluorescence were made on unexposed skin sites during the first 5 h after drug injection. Immediate responses to PDT included erythema induced by 458 nm light and blanching induced by 690 nm light. Delayed reactions included edema on the day of exposure, purpura at 24 h, eschar by day 2 or 3, and scar by the end of follow-up. The threshold fluence for immediate responses correlated strongly with the threshold fluence for delayed reactions. The induction of threshold purpura on day 1 was a reliable index for skin phototoxicity that led to necrosis. The minimum purpura dose on day 1 after irradiation increased exponentially with the interval between drug injection and irradiation, independent of irradiation wavelength, for all drug doses. The action spectrum for threshold purpura mimics closely the absorption spectrum of BPD-MA. The in vivo drug fluorescence correlated with skin phototoxicity, thus allowing predictive dosimetry. This model system defines the safety limits for skin phototoxicity of PDT with BPD-MA.

Efficacy of Suprachoroidal–Transretinal Stimulation in a Rabbit Model of Retinal Degeneration

“…17 We also chose a red LED for the light source because the LED light does not generate heat as easily as do other light sources, and 630 nm is the peak excitation wavelength of verteporfin. 20,21 We then conducted another pilot study to develop a retinal degeneration model with verteporfin and a red LED. We changed the dose of verteporfin (0.24, 0.47, and 0.96 mg/kg), total irradiation time (45 and 90 minutes), irradiation direction (1 and 3 directions) and distance (0 and 15 mm), and finally succeeded in creating substantial damage to the outer retinal layers with a dose of 0.47 mg/kg verteporfin and irradiation from 3 directions for 30 minutes, each when the red LED was placed just in front of the diffuser contact lens.…”

Photodynamic therapy in the treatment of intracranial gliomas: A review of current practice and considerations for future clinical directions

“…This can be achieved by an appropriate photon source distribution within the limits governed by the optical properties of the tissue. [31][32][33] Additional selectivity is provided by the pharmacokinetics of the photosensitizers, leading to a local di®erential accumulation and retention in GBM tumor tissue versus normal intracranial tissues to provide selectivity particularly in BAT seeded with micro in¯ltrates. 34,35 For ALA, glioblastoma shows a larger synthesis and retention of PpIX compared to the normal surrounding brain tissue.…”

Vascular effects of photodynamic and pulsed dye laser therapy protocols

“…We selected benzoporphyrin derivative (BPD) monoacid ring A as the photosensitizer due to initial vascular predominance [19-22], proven safety and efficacy, and photosensitivity of relatively short duration [13,23]. Yellow light was selected due to high BPD absorption and limited depth of vascular injury.…”