5-Aminolevulinic-acid-mediated Photodynamic Diagnosis Enhances the Detection of Peritoneal Metastases in Biliary Tract Cancer in Mice
5-Aminolevulinic-acid-mediated Photodynamic Diagnosis Enhances the Detection of Peritoneal Metastases in Biliary Tract Cancer in Mice
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DOI：
10.21873/invivo.11145
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发表时间：
2017-09-01
期刊：
影响因子：
2.3
通讯作者：
Hirano, Satoshi
中科院分区：
文献类型：
--
作者：
Kushibiki, Toshihiro;Noji, Takehiro;Hirano, Satoshi
背景/目的：先前关于5-氨基酮戊酸介导的光动力学诊断（5-ALA PDD）的准确性的研究已被报道用于各种癌症和脑外科手术。然而，胆道癌是罕见的。因此，5-ALA PDD尚未在胆道癌中得到充分评价。小的胆道癌病变如腹膜转移、肝转移和淋巴结转移是胆道癌患者的阴性预测因子。该探索性研究的目的是确定5-ALA PDD是否可以检测胆管癌小鼠模型中的小胆管癌病变。材料与方法：使用胆管癌细胞系（TFK-1、HuCCT-1、G415、HuH 28、SSP 25、RBE、KKU 055和KKU 100）和正常人真皮成纤维细胞来评估原卟啉IX（PpIX）的体外积累。使用两种细胞系（TFK-1和HuCCT-1）建立皮下肿瘤小鼠。5-腹膜内给予ALA（250 mg/kg），3小时后进行荧光5ALA-PDD以评价肿瘤PpIX积累。通过腹腔注射TFK-1细胞建立小鼠腹膜播散性结节模型。4周后，腹腔内给予5-ALA，并在给药后3小时进行5-ALA-PDD以评估播散结节中PpIX的积累。通过苏木精和伊红染色证实肿瘤和结节中存在肿瘤细胞。结果：与非癌细胞系相比，胆管癌细胞系中PpIX积累增加。PpIX积累导致所有皮下肿瘤中的强荧光信号。在小鼠腹膜播散模型中，使用5-ALA-PDD可清楚地看到在白色光下无法检测到的微播散结节（< 1 mm）。结论：5-ALA PDD可用于胆道癌的诊断和胆道癌小鼠模型中小的腹膜转移病灶的检测。展望5-ALA PDD治疗胆道恶性肿瘤的临床研究和应用前景。
Background/Aim: Previous studies on the accuracy of 5-aminolevulinic-acid-mediated photodynamic diagnosis (5-ALA PDD) have been reported for various cancers and brain surgery. However, biliary tract cancer is rare. Therefore, 5-ALA PDD has not been fully evaluated in biliary tract cancers. Small biliary tract cancer lesions such as peritoneal dissemination, liver metastases, and lymph node metastases are negative prognosticators in patients with biliary cancer. The purpose of this exploratory study was to determine if 5-ALA PDD could detect small biliary tract cancer lesions in murine models of biliary cancers. Materials and Methods: Biliary cancer cell lines (TFK-1, HuCCT-1, G415, HuH28, SSP25, RBE, KKU055 and KKU100) and Normal human dermal fibroblast cells were used to evaluate protoporphyrin IX (PpIX) accumulation in vitro. Subcutaneous tumor mice were established using two cell lines (TFK-1 and HuCCT-1). 5-ALA (250 mg/kg) was administered intraperitoneally, and fluorescent 5ALA-PDD was performed 3 h later to evaluate tumoral PpIX accumulation. A murine peritoneal disseminated nodule model was established by intraperitoneal injection of TFK-1 cells. Four weeks later, 5-ALA was administered intraperitoneally, and 5-ALA-PDD was performed 3 h post administration to evaluate PpIX accumulation in the disseminated nodules. The presence of tumor cells in tumors and nodules was confirmed by haematoxylin and eosin staining. Results: Compared TO non-cancerous cell lines, PpIX accumulation was increased in biliary tract cancer cell lines. PpIX accumulation led to a strong fluorescent signal in all subcutaneous tumors. In the murine model of peritoneal dissemination, microdisseminated nodules (< 1 mm) that could not be detected under white light were clearly visible using 5-ALA-PDD. Conclusion: 5-ALA PDD was useful for diagnosis of biliary tract cancer and detection of small peritoneal metastatic lesions in murine models of biliary cancers. Clinical studies and applications of 5-ALA PDD for biliary tract cancer are expected in the future.