Comparison of aminolevulinic acid- and hexylester aminolevulinate-induced protoporphyrin IX fluorescence for the detection of ovarian cancer in a rat model.

OBJECTIVES: This study set out to compare the photodetection of peritoneal micrometastases in an ovarian cancer model following administration of two precursors of protoporphyrin IX (PpIX): 5-aminolevulinic acid (ALA) and hexylester aminolevulinate (He-ALA). METHODS: ALA or He-ALA (100 mg/kg) was injected into the peritoneal cavity of 16 rats with induced peritoneal metastases of ovarian cancer. Two hours later, the tumors were visualized laparoscopically using both white light for standard exploration and blue light for fluorescence. Peritoneal micrometastases were counted. Fluorescence intensities of tumoral and normal surrounding tissues were compared. The distribution of PpIX throughout the peritoneum was studied on frozen biopsies using fluorescence microscopy and correlated with pathological findings. RESULTS: The number of micrometastases detected by the fluorescence blue mode was significantly higher (p < 0.05) than with standard white light for both ALA (235 versus 198) and He-ALA application (248 versus 199). The mean fluorescence intensity ratio between tumor and normal surrounding tissue was significantly (p < 0.05) higher for He-ALA (1.55 +/- 0.1) compared to ALA (1.45 +/- 0.1). Fluorescence microscopy confirmed that the PpIX fluorescence remained limited to cancer cells. Macroscopically fluorescing nodules were histopathologically confirmed as malignant. CONCLUSION: He-ALA is an excellent precursor for PpIX synthesis, giving the highest PpIX fluorescence contrast between normal and tumoral peritoneal tissues. Imaging with He-ALA improves the detection of peritoneal metastases compared to ALA.