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Hemoporfin-mediated photodynamic therapy on normal vasculature: implications for phototherapy of port-wine stain birthmarks

机译:血卟啉介导的光动力疗法对正常脉管系统的影响:对光斑痣胎记的光疗的意义

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摘要

>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 run 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 inj ection 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.>Conclusions: The experimental data collectively suggest that Hemoporfin-mediated PDT can achieve persistent vascular shutdown of normal microvasculature. However, compared with our previous data using Talaporfin Sodium as photosensitizer, Hemoporfin-mediated PDT is less efficient and requires a considerably longer (~four times) irradiation time.>Relevance for patients: Patients with PWS lesions may benefit from the advantages that PDT potentially offers over conventional PDL therapy. PDT potentially is safer for patients of all skin types and more effective at treatment of recalcitrant lesions. Although clinical data suggest that Hemoporfin-mediated PDT is a promising alternative to PDL therapy, our results suggest that additional study of other photosensitizers is warranted.
机译:>背景:目前,使用脉冲染料激光(PDL)结合表皮的瞬时冷却来处理酒斑(PWS)胎记。由于血管内血红蛋白的吸收,PDL治疗方案利用短脉冲光(585或595运行波长)选择性加热微血管。尽管大多数患者对PDL治疗有反应,但很少有患者完全清除PWS。 PWS PDL治疗的替代治疗选择是光动力治疗(PDT)。研究小组报告了用于PWS的PDT的各种光敏剂,包括血红素,苯并卟啉衍生物一元酸环A和他拉泊芬钠。>目的:我们的目的是利用已建立的临床前体内模型评估Hemoporfin进行光动力疗法(PDT)的效果,以实现持续的血管关闭。>方法:为监测微脉管系统,在24只成年小鼠上手术安装了一个背窗室。 PDT激发源发出150mW的532nm光,辐照度为100mW / cm 2 。进行血红蛋白的眼眶后注射(2 mg / kg)以将药物输送到血液中。注射后立即开始激光照射。为了监测响应PDT的血流动力学,我们使用了激光散斑成像。我们采用剂量反应实验设计研究了Hemoporfin介导的PDT在PDT后第7天观察到的实现持续性血管关闭的功效。>结果:我们观察到了对PDT的四种总体血流动力学反应:(1)在低辐射照射下,我们没有观察到任何持续的血管关闭; (2)在中等辐射照射下,我们观察到延迟的血管关闭作用,血管结构发生了显着变化; (3)在中等辐射照射下,我们观察到急性血管关闭效应,逐渐恢复血流,血管结构无明显变化; (4)在高辐射照射下,我们观察到在整个7天的监测期内持续存在急性血管关闭,并且血管结构没有变化。通过光剂量响应分析,我们估计特征性辐射暴露为359 J / cm 2 ,这是实现PDT后第7天观察到的持续性血管关闭所必需的。>结论:实验数据共同表明,血红素介导的PDT可以实现正常微脉管系统的持续性血管关闭。但是,与我们以前使用塔拉泊芬钠作为光敏剂的数据相比,血红素介导的PDT效率较低,并且需要更长的照射时间(约四倍)。>与患者的相关性:PWS病变患者可能会受益与传统的PDL治疗相比,PDT具有的优势。 PDT对于所有皮肤类型的患者而言都可能更安全,并且在顽固性病变的治疗上可能更有效。尽管临床数据表明Hemoporfin介导的PDT是替代PDL治疗的有希望的替代方法,但我们的结果表明,有必要对其他光敏剂进行进一步研究。

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