Fluorescence diagnosis of metastatic lymph nodes using 5-aminolevulinic acid (5-ALA) in a mouse model of colon cancer.
BACKGROUND
Lymph node metastasis is one of the most critical prognostic factors in patients with colorectal cancer. Although regional lymph nodes should be surgically resected and pathologically examined, techniques for the intraoperative diagnosis of lymph node metastasis remain to be well established. Fluorescence diagnosis using 5-aminolevulinic acid (5-ALA) is a promising technique for evaluating various malignancies. After exogenous administration of 5-ALA, protoporphyrin IX (PPIX) accumulates in malignant cells and can be detected as red fluorescence. In this study, we investigated the usefulness of fluorescence diagnosis using 5-ALA for the detection of lymph node metastasis in a mouse model of colon cancer.


METHODS
An orthotopic colon cancer model was prepared by inoculating the cecal wall of nude mice with HCA7, a human colon adenocarcinoma cell line. After 3 wk, 40 mg/kg of 5-ALA was administered intraperitoneally (IP) or orally (PO). Fluorescence diagnosis with a D-Light System (Karl Storz) was then performed after 3 or 6 h.


RESULTS
In the IP group, PPIX fluorescence was detected in metastatic lymph nodes as well as in other malignant lesions, including primary tumors and abdominal implantations, while non-metastatic nodes were fluorescence-negative. In contrast, no obvious fluorescence was detected in cancerous tissues in the PO group.


CONCLUSIONS
PPIX fluorescence induced by intraperitoneal injection of 5-ALA allows metastatic lymph nodes to be accurately diagnosed in this mouse model. This technique may facilitate the intraoperative diagnosis of lymph node metastases from colon cancer in a clinical setting.
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. skato77@kuhp.kyoto-u.ac.jp
Shigeru
S
Kato
Junichiro
J
Kawamura
Kenji
K
Kawada
Suguru
S
Hasegawa
Yoshiharu
Y
Sakai
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000556:secondary* / Q000601:surgery; D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000556:secondary* / Q000601:surgery; D005260:Female; D005453:Fluorescence; D006801:Humans; D007274:Injections, Intraperitoneal; D007432:Intraoperative Period; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017319:Photosensitizing Agents / Q000494:pharmacology
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid