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首页> 外文会议>Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems VIII >Pharmacokinetics and efficacy of 5-aminolaevulinic acid for endovascular photodynamic therapy in a swine model
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Pharmacokinetics and efficacy of 5-aminolaevulinic acid for endovascular photodynamic therapy in a swine model

机译：5-氨基乙酰戊酸在猪模型中的血管内光动力疗法的药代动力学和功效

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Abstract: Vascular smooth muscle cells (VSMC) are known to be important in restenosis and photodynamic therapy (PDT) has been shown experimentally to deplete the VSMC population in small animal studies. We aimed to investigate the pharmacokinetics of 5- aminolaevulinic acid (5-ALA) and to see if endovascular PDT was feasible in a large animal model. Large White pigs (15 - 20 Kg) were photosensitized with 5-ALA at a concentration of 60 and 120 mg/Kg. Arterial biopsies were taken at intervals between 30 mins and 24 hours and snap frozen in liquid nitrogen. Frozen sections were analyzed using a CCD camera and PpIX activity assessed by computing pixel counts for intima, media and adventitia at each time point. Based on the above results 8 pigs were treated with PDT at 1.5, 2.5 or 6 hours following 5-ALA administration. Iliac segments were then illuminated with 50 J/cm$+2$/, 635 nm wavelength light via a 4 mm transparent PTA balloon. Animals were culled at 3 days and the above segments pressure perfused in situ with 4% formyl saline, before being excised and fixed. Fluorescence peaked in the adventitia at 1.5 hours, was minimal at 2.5 hours and peaked in the media at 6 hours post 5-ALA. Of the second series of 8 pigs, all animals survived to culling and all treated arteries remained patent. Histological sections stained with H&E were examined and medial VSMC's counted in 4 individual high power fields per section. The mean VSMC count per HPF for PDT treated segments was 16, 51 and 12 at 1.5, 2.5 and 6 hours respectively. VSMC counts in ALA alone controls and light alone controls were 115 and 103 respectively (p less than 0.0001). Endovascular delivery of light to 5-ALA sensitized animals is therefore feasible and was not associated with any complications. !21
机译：摘要：已知血管平滑肌细胞（VSMC）在再狭窄中很重要，在小动物研究中，实验证明光动力疗法（PDT）可以耗尽VSMC种群。我们旨在研究5-氨基戊酸（5-ALA）的药代动力学，并观察在大型动物模型中血管内PDT是否可行。用5-ALA以60和120 mg / Kg的浓度对大白猪（15-20 Kg）进行光敏。每隔30分钟至24小时进行一次动脉活检，并在液氮中速冻。使用CCD相机分析冷冻切片，并通过计算每个时间点的内膜，中膜和外膜像素计数评估PpIX活性。基于以上结果，在给予5-ALA后1.5、2.5或6小时用PDT处理了8头猪。然后通过4mm透明PTA气球用50J / cm 2 +2 3 635nm波长的光照射节。在第3天将动物剔除并在切下并固定之前，将上述片段用4％甲酰盐水原位灌注。 5-ALA后，外膜在1.5小时达到峰值，在2.5小时达到最小，而在培养基中则在6小时达到峰值。在第二批的8头猪中，所有动物都幸免于难，并且所有经过治疗的动脉都保持了专利。检查用H＆E染色的组织学切片，并在每个切片的4个单独的高倍视野中计数内侧VSMC。 PDT处理段的每个HPF平均VSMC计数分别为1.5、2.5和6小时的16、51和12。仅ALA对照和仅光对照的VSMC计数分别为115和103（p小于0.0001）。因此，向5-ALA致敏的动物向血管内输送光是可行的，并且没有任何并发​​症。 ！21

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