5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges

5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges
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DOI:
10.3390/ijms23126478
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发表时间:
2022-06-09
影响因子:
5.6
通讯作者:
Tanaka, Hideo
Tanaka, Hideo
中科院分区:
生物学2区
文献类型:
--
作者:
Harada, Yoshinori;Murayama, Yasutoshi;Takamatsu, Tetsuro;Otsuji, Eigo;Tanaka, Hideo

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5-氨基乙酰丙酸(5-ALA)是一种天然氨基酸,是血红素和叶绿素的前体。外源性给予的5-ALA被代谢成原卟啉IX(PpIX)。PpIX在癌细胞中积累是因为亚铁螯合酶的活性低,亚铁螯合酶是一种将PpIX代谢为血红素的酶。癌细胞中5-ALA内流转运蛋白如肽转运蛋白1/2的高表达也增强PpIX的产生。由于PpIX在用蓝/紫光激发时辐射红色荧光,因此5-ALA已用于各种肿瘤的可视化。5-ALA光动力学诊断(PDD)已被证明可以提高高级别胶质瘤和非肌层浸润性膀胱癌的肿瘤切除率。然而,5-ALA PDD作为诊断方法仍然是一个挑战,因为在肿瘤仅发射弱信号的情况下,组织自体荧光干扰PpIX信号,而非肿瘤性病变(如炎症部位)倾向于发射PpIX荧光。在这里,我们回顾了目前的大纲5-ALA PDD和策略,以提高其诊断适用性的肿瘤检测,重点是光学技术和5-ALA代谢途径在两个可行的和坏死的肿瘤组织。
5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 5-ALA photodynamic diagnosis (PDD) has been shown to improve the tumor removal rate in high-grade gliomas and non-muscular invasive bladder cancers. However, 5-ALA PDD remains a challenge as a diagnostic method because tissue autofluorescence interferes with PpIX signals in cases where tumors emit only weak signals, and non-tumorous lesions, such as inflammatory sites, tend to emit PpIX fluorescence. Here, we review the current outline of 5-ALA PDD and strategies for improving its diagnostic applicability for tumor detection, focusing on optical techniques and 5-ALA metabolic pathways in both viable and necrotic tumor tissues.
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