Laparoscopic fluorescence detection of ovarian carcinoma metastases using 5‐aminolevulinic acid‐induced protoporphyrin IX

Abstract

BACKGROUND The aim of the current clinical study was to evaluate the in vivo fluorescence detection of ovarian carcinoma metastases in a second‐look laparoscopic procedure after intraperitoneally applied 5‐aminolevulinic acid (ALA). METHODS Five hours before laparoscopic surgery, ALA was applied intraperitoneally via short infusion in a concentration of 30 mg/kg bodyweight in a sterile, 1% solution. Application of ALA resulted in the endogenous production of the fluorescent photosensitizer, protoporphyrin IX (PP IX). The Combilight PDD 5133 system served as a light source, permitting the switch from white light mode to blue light mode to excite the PP IX accumulated in the ovarian tissue specimens. By means of blue light illumination, intraperitoneally located red fluorescent lesions, which were suspected to be metastases, underwent a biopsy. In addition, several biopsy specimens were taken from nonfluorescent areas of the peritoneal cavity. RESULTS In 13 of 29 patients, ovarian carcinoma was confirmed histologically or cytologically. In 12 of these patients, metastases were visible by red fluorescence. In total, 123 biopsies were performed. Comparison of histologic assessment of the biopsy specimens with the fluorescence detection showed that strong red fluorescence had a sensitivity of 92% for detecting tumor tissue on specimens. In only 2% of all biopsy specimens was endometriosis observed in benign tissue specimens using fluorescence. In four of 13 patients with ovarian carcinoma, lesions were detected under fluorescence, which were not observed under white light illumination. CONCLUSIONS Laparoscopic fluorescence detection of endogenous PP IX after intraperitoneal application of ALA may provide a higher sensitivity of finding peritoneal metastases of epithelian ovarian carcinoma compared with conventional laparoscopy. Direct visualization of in vivo fluorescence after ALA application may improve the early detection of intraperitoneal ovarian carcinoma micrometastases. The high tissue selectivity of PP IX accumulation in tumor tissue specimens also offers the opportunity for therapeutic approaches using photodynamic therapy in the future. Cancer 2004. © 2004 American Cancer Society.

In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring

“…Upon wavelength-specific activation of the PS, fluorescence emission for diagnostic imaging and cytotoxic species (through intersystem crossing to the triplet state) for tissue destruction can both be produced. Previous studies that used PS (ALA-induced protoporphyrin IX and/or hexaminolaevulinate) for OvCa imaging were successful in detecting significantly more lesions than white light imaging (Chan et al, 2002;Ludicke et al, 2003;Loning et al, 2004), with a ratio of fluorescence intensity of neoplastic to normal tissues of B4 (Chan et al, 2002;Ludicke et al, 2003). The average size of the optically biopsied metastatic lesions was 1.0 mm (range: 0.3 -2.5) compared with 1.5 mm (range: 0.5 -2.9) with white light illumination (Chan et al, 2002).…”

Talaporfin-mediated photodynamic therapy for peritoneal metastasis of gastric cancer in an in vivo mouse model: Drug distribution and efficacy studies

“…With regard to 5-aminolevulinic acids (ALA), numerous studies have reported that 5-ALA is useful for photodynamic diagnosis (PDD) of various malignant tumors (26)(27)(28). Several reports have shown promising preliminary results of 5-ALAmediated photodynamic therapy (PDT) in the treatment of malignant tumors in the abdominal cavity (29,30).…”

Intraoperative Navigation and Fluorescence Imagings in Malignant Glioma Surgery

“…Clinical use of 5-ALA for photodynamic therapy (PDT) or PDD has also been reported for lung cancer, ovarian cancer, and bladder cancer. [36][37][38] In the USA, it has been used with the approval of the Food and Drug Administration (FDA) as a therapeutic drug for solar keratosis, while its use has not yet been approved by the pharmaceutical authority in Japan, and it is only used after obtaining approval of the ethics committee of the respective institutes. The tumor tissue concentration of the fluorescent dye peaks at 2-6 hours after oral administration, and disappears by 12 hours.…”