Pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate in patients with cervical intraepithelial neoplasia
Pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate in patients with cervical intraepithelial neoplasia
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DOI：
10.1016/j.ajog.2007.07.045
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发表时间：
2008-03-01
影响因子：
9.8
通讯作者：
Soergel, Philipp
中科院分区：
文献类型：
--
作者：
Hillemanns, Peter;Wang, Xiuli;Soergel, Philipp
目的：光动力疗法对于育龄期CIN患者具有微创门诊治疗的潜力。本研究的目的是研究在宫颈上皮内瘤变（CIN）患者局部应用六聚己油酰丙酸（HAL）后卟啉合成的药代动力学和选择性。研究设计：24名CIN 1-3的女性在手术前5- 720分钟局部接受4 mmol/L或10 mmol/L HAL溶解于可耐热pluronic f127凝胶中。显微荧光模式通过635 nm的离体荧光光谱进行定量，并通过冰冻切片的数字图像分析进行半定量。结果：在4和10 mmol/L HAL时，卟啉荧光强度随时间增加，在CIN和正常上皮中，在180-540分钟的应用间隔后达到峰值。然而，与正常组织相比，CIN的峰值更为明显。10 mmol/L的荧光强度显著高于4 mmol/L的荧光强度（P < 0.05）。最大强度通常在上皮下层检测到。结论：HAL是一种很有前途的荧光诊断分子。对于进一步的治疗研究，我们建议在CIN光动力治疗前300-540分钟应用10 mmol/L HAL。
OBJECTIVE: Photodynamic therapy has the potential of a minimal invasive outpatient procedure for CIN patients at reproductive ages. The purpose of this study was to examine the pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate (HAL) in patients with cervical intraepithelial neoplasia (CIN).STUDY DESIGN: Twenty-four women with CIN 1-3 received 4 mmol/L or 10 mmol/L HAL dissolved in thermolabile pluronic F 127 gel topically 5- 720 minutes before surgical conization. The microscopic fluorescence pattern was quantified by ex vivo fluorescence spectroscopy at a wavelength of 635 nm and semiquantitatively by digital image analysis from cryosections.RESULTS: With 4 and 10 mmol/L HAL, porphyrin fluorescence intensity increased over time, reaching a peak after 180-540 minutes application intervals in CIN and normal epithelium. However, the peak was much more pronounced in CIN than in normal tissues. The fluorescence intensity with 10 mmol/L was significantly higher than that with 4 mmol/L in CIN tissues (P < .05). Maximum intensity could generally be detected in the lower layer of the epithelium.CONCLUSION: HAL seems to be a promising molecule for fluorescence diagnosis. For further treatment studies, we recommend application of 10 mmol/L HAL 300-540 minutes before photodynamic therapy in CIN.