Photodynamic diagnosis of peritoneal metastasis in human pancreatic cancer using 5‑aminolevulinic acid during staging laparoscopy

Abstract

Peritoneal metastasis is an important prognostic factor for pancreatic cancer. The present study evaluated the possibility of diagnosing peritoneal metastasis by a photodynamic diagnosis using 5-aminolevulinic acid (5-ALA-PDD). In vitro, protoporphyrin IX (PpIX) accumulation was examined in the AsPC-1-GFP cell line following 5-ALA hydrochloride administration. In vivo, AsPC-1-GFP cells were injected into the peritoneal cavities of mice. Three weeks later 5-ALA hydrochloride was intraperitoneally administered to the mice. The peritoneal nodules were observed under fluorescence excitation. A total of 34 patients were enrolled in the present study who were clinically diagnosed with pancreatic malignancy. 5-ALA hydrochloride was orally administered to the patients prior to surgery. During the operation the abdominal cavity was observed under white light and fluorescence. In vitro and in vivo, it was confirmed that PpIX-induced red fluorescence. In 9 patients peritoneal nodules suspected to be peritoneal metastasis were observed under white light. In 4 of the 9 patients nodules were detected on the basis of the fluorescence images. Fluorescent nodules were histopathologically diagnosed as metastatic. In the present study it was confirmed that 5-ALA-PDD holds promise for the rapid diagnosis of peritoneal metastasis in patients with pancreatic cancer.

Solubilization of Hexyl Aminolevulinate by Surfactants for Tumor Fluorescence Detection

“…Compared with those naturally fluorescent molecules, ALA could provide highly selective tumor fluorescence imaging because tumoral cells tend to exhibit higher levels of PpIX than normal cells after ALA administration (38,39). 5‐ALA has been used in in vitro and in vivo PDD of pancreatic cancer (40,41).…”

Uptake Transporters of the SLC21, SLC22A, and SLC15A Families in Anticancer Therapy—Modulators of Cellular Entry or Pharmacokinetics?

“…ALA-mediated photodynamic diagnosis (ALA-PDD) and fluorescence-guided surgery (FGS) are additional applications which have been approved for brain surgery to visualize tumor tissue during tumorectomy of malignant gliomas [213]. In recent clinical trials, the use of ALA-PDD was successfully expanded to imaging of bladder and gastric cancers as well as peritoneal metastases of different tumor origin such as ovarian, pancreatic, or gastric cancers [214][215][216]. In terms of pharmacokinetics, it has been shown that, when ALA is administered orally, intravenously, or topically, it is readily taken up by cells with an accumulation primarily in epithelia [217].…”

Photodynamic Diagnosis and Therapy for Peritoneal Carcinomatosis: Emerging Perspectives

“…Compared to conventional cytoreductive surgery under white light, PDD presents a promising modality to improve the detection rate of micrometastases with high sensitivity and specificity [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. However, despite these promising results, PDD remains an experimental diagnostic tool which is not yet widely applied.…”

“…In this section, we present an overview of relevant clinical trials published since 2010 and discuss their major findings. Almost all trials used ALA, given 2–4 h preoperatively with an oral dosage ranging from 10 to 20 mg/kg [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Exposure to sunlight was avoided during 24 h after administration to prevent phototoxicity, and all studies report the absence of unacceptable morbidity.…”

“…One study reported on PDD in 34 patients of pancreatic cancer, in which oral ALA was given 3 h prior to cytoreductive surgery at a dose of 20 mg/kg. Suspicious lesions were identified under white light, were positively identified using PDD, and were then confirmed to be metastatic lesions, representing a sensitivity and specificity of 100% [ 40 ].…”