Hemoporfin-mediated photodynamic therapy on normal vasculature: implications for phototherapy of port-wine stain birthmarks
Journal Title: Journal of Clinical and Translational Research - Year 2016, Vol 2, Issue 3
Abstract
Background: Port-wine stain (PWS) birthmarks currently are treated using a pulsed dye laser (PDL) combined with transient cooling of the epidermis. PDL treatment protocols utilize short pulses of light (585 or 595 nm wavelength) to heat selectively the microvasculature due to absorption by intravascular hemoglobin. Although most patients respond to PDL therapy, few experience complete removal of the PWS. An alternate treatment option to PDL therapy of PWS is photodynamic therapy (PDT). Research groups have reported on various photosensitizers for PDT of PWS, including Hemoporfin, Benzoporphyrin Derivative monoacid ring A, and talaporfin sodium. Aim: Our aim was to evaluate, with an established preclinical in-vivo model, the efficacy of photodynamic therapy (PDT) with Hemoporfin to achieve persistent vascular shutdown. Methods: To monitor the microvasculature, a dorsal window chamber was surgically installed on 24 adult mice. The PDT excitation source emitted 150mW of 532nm light, with an irradiance of 100mW/cm2 . A retroorbital injection of Hemoporfin (2 mg/kg) was performed to deliver the drug into the bloodstream. Laser irradiation was initiated immediately after injection. To monitor blood-flow dynamics in response to PDT, we used laser speckle imaging. We employed a dose–response experimental design to study the efficacy of Hemoporfin-mediated PDT to achieve persistent vascular shutdown observed on Day 7 after PDT. Results: We observed four general hemodynamic responses to PDT: (1) At low radiant exposures, we did not observe any persistent vascular shutdown; (2) at intermediate radiant exposures, we observed delayed vascular shutdown effect with significant change to the vascular structure; (3) at intermediate radiant exposures, we observed an acute vascular shutdown effect with gradual restoration of blood flow and no significant changes to the vascular structure; and (4) at high radiant exposures, we observed acute vascular shutdown that persisted during the entire 7-day monitoring period, with no change in vascular structure. With light dose–response analysis, we estimated a characteristic radiant exposure of 359 J/cm2 that was required to achieve persistent vascular shutdown observed on Day 7 after PDT.
Authors and Affiliations
Wesley J. Moy, Gang Ma, Kristen M. Kelly, Bernard Choi
Keywords
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