Fluorescent detection of peritoneal metastasis in human colorectal cancer using 5-aminolevulinic acid

Abstract

A precise diagnosis of peritoneal dissemination is necessary to determine the appropriate treatment strategy for colorectal cancer. However, small peritoneal dissemination is difficult to diagnose. 5-aminolevulinic acid (5-ALA) is an intermediate substrate of heme metabolism. The administration of 5-ALA to cancer patients results in tumor-specific accumulation of protoporphyrin IX (PpIX), which emits red fluorescence with blue light irradiation. We evaluated the usefulness of photodynamic diagnosis (PDD) using 5-ALA to detect the peritoneal dissemination of colorectal cancer. EGFP-tagged HT-29 cells were injected into the peritoneal cavity of BALB/c nude mice. After 2 weeks, the mice were given 5-ALA hydrochloride, and metastatic nodules in the omentum were observed with white light and fluorescence images. Twelve colorectal cancer patients suspected to have serosal invasion according to preoperative computed tomography (CT) were enrolled in this study. 5-ALA (15-20 mg per kg body weight) was administered orally to the patients 3 h before surgery. The abdominal cavity was observed under white light and fluorescence. Fluorescence images were analyzed with image analysis software (ImageJ 1.45s, National Institutes of Health, Bethesda, MD, USA). The mice developed peritoneal disseminations. The observed 5-ALA-induced red fluorescence was consistent with the EGFP fluorescent-positive nodules. Peritoneal dissemination was observed with conventional white light imaging in 8 patients. All nodules suspected as being peritoneal dissemination lesions by white light observation were similarly detected by ALA-induced fluorescence. In 1 patient, a small, flat lesion that was missed under white light observation was detected by ALA-induced fluorescence; the lesion was pathologically diagnosed as peritoneal metastasis. In the quantitative fluorescence image analysis, the red/(red + green + blue) ratio was higher in the metastatic nodules compared to the non-metastatic sites of the abdominal wall, fat and liver. We demonstrated better diagnostic accuracy using 5-ALA-PDD compared to conventional laparoscopy in patients with colorectal cancer. 5-ALA-PDD is a promising candidate method for diagnosing peritoneal dissemination of colorectal cancer.

Incidence and treatment of recurrent disease after cytoreductive surgery and intraperitoneal chemotherapy for peritoneally metastasized colorectal cancer: A systematic review

“…In vivo fluorescence facilitates visualization of peritoneal metastases and enables direct assessment of margin status. 39,40 In PC of ovarian origin, this technique has proven to be safe and feasible, although long term results are yet to be revealed. 41 Secondly, animal experiments testing different drug delivery systems to more effectively administer chemotherapy, such as drug eluding beads, hydrogels or microspheres show promising results in increasing chemotherapeutic efficacy, although no clinical experience is yet available.…”

Next Generation intraoperative Lymph node staging for Stratified colon cancer surgery (GLiSten): a multicentre, multinational feasibility study of fluorescence in predicting lymph node-positive disease

“…51 A total of 12 patients were selected on the basis of suspected peritoneal disease on CT scans and, in eight patients (66.7%), fluorescence of peritoneal metastases was shown. Unfortunately, this study did not comment on fluorescence of the primary tumour, LNs or any other metastatic deposits that would allow comparison with our study findings.…”

Stable archaeal tetraether lipid liposomes for photodynamic application: transfer of carboxyfluorescein to cultured T84 tumor cells

“…More specifically, we want to find out whether TEL liposomes can be used for liposomal photodynamic diagnosis (PDD) and therapy (PDT), which have attracted great attention during the last 10 years. The benefits of 5-aminolevulinic acid (5-ALA) PDD in colorectal oncology -including abdominal metastases -have been reported by Kondo et al 8 Furthermore, 5-Ala PDD is widely performed in urological oncology with transurethral fluorescence cystoscopy, especially for the detection of small bladder tumors 9 and urothelial premalignant lesions, 10 as well as in prostatectomy.…”