IN-VIVO DETECTION OF METASTATIC OVARIAN-CANCER BY MEANS OF 5-AMINOLEVULINIC ACID-INDUCED FLUORESCENCE IN A RAT MODEL

Study Objectives. To determine the feasibility of macroscopic visualiz ation of small ovarian cancer metastases in vivo by fluorescence after intra venous administration of 5-aminolevulinic acid (ALA); to assess the time alter drug injection when fluorescence of small metastases i s maximum; and to correlate macroscopic in vivo fluorescence with both microscopic ex vivo fluorescence and histologic findings. Design. Con trolled animal study (Canadian Task Force classification I). Setting. University-based facility Subjects. Twenty-four healthy, female Fische r rats. Intervention. Diffuse peritoneal metastatic cancer was induced in Fischer 344 rats by intraperitoneal injection of 1 million syngene ic ovarian cancer cells (NuTu-19). Four weeks after induction ALA100 m g/kg was injected intravenously, and diagnostic laparotomy was perform ed 1, 3, 6, or 9 hours there after. Measurements and Main Results. The peritoneal cavity was illuminated with the Wood's lamp (ultraviolet l ight). Fluorescence was determined by direct visualization and compare d with a calibrated fluorescent disk. Tissues Mere collected sectioned , and examined by fluorescence and conventional light microscopy. With in 1 to 3 hours after intravenous injection of ALA, in vivo fluorescen ce of tumor nodules (diameter 0.4-5.0 mm) was macroscopically visible. Tumor-free peritoneum did not show fluorescence and was significantly distinguishable from cancer nodules. Fluorescence from intestinal tis sues was comparable with tumor nodules. Microscopic fluorescence analy sis showed similar values for tumor nodules and peritoneum. Stained hi stologic specimens of peritoneal surface revealed a superficial layer of cancer cells responsible for fluorescence. The time course of the f luorescence curve in the intestine peaked twice, at 1 and 6 hours alte r ALA injection. Macroscopically fluorescing nodules were histology co nfirmed as malignant. Conclusions. Fluorescence detection of small can cer nodules after intravenous injection of ALA is feasible for nodules smaller than 0.5 mm on the peritoneum. One to 3 hours after drug inje ction is optimal for diagnosis of metastases.