In vivo fluorescence detection of ovarian cancer in the NuTu-19 epithelial ovarian cancer animal model using 5-aminolevulinic acid (ALA).
The purpose of this study was to determine whether in vivo fluorescence detection of protoporphyrin IX (PpIX) could be used to identify intraperitoneal micrometastases of epithelial ovarian carcinoma after application of 5-aminolevulinic acid (ALA). ALA was applied intraperitoneal at different concentrations (25, 50, and 100 mg/kg) and iv (100 mg/kg) to immunocompetent Fischer 344 rats bearing a syngeneic epithelial ovarian carcinoma. At different time intervals after ALA administration (1.5, 3, and 6 hr) the peritoneal cavity was illuminated with ultraviolet (uv) light. In vivo fluorescence of PpIX initially was determined by direct visualization. Subsequently ex vivo measurements were made with a slow-scan, thermoelectrically cooled CCD camera. Red in vivo fluorescence was observed in ovarian micrometastases smaller than 0.5 mm in 100% of the ALA-administered animals independent of time interval, drug concentration, or route of administration. The intensity of the fluorescence was concentration dependent as strong fluorescence was consistently found only above 25 mg/kg ALA. Ex vivo tumor to peritoneum fluorescence yield peaked 3 hr after administration of a 100 mg/kg intraperitoneal dose. Direct visualization of in vivo fluorescence after ALA application may improve the detection of intraperitoneal ovarian cancer micrometastases.
Major
A L
AL
Beckman Laser Institute, University of California, Irvine, 92715, USA.
Rose
G S
GS
Chapman
C F
CF
Hiserodt
J C
JC
Tromberg
B J
BJ
Krasieva
T B
TB
Tadir
Y
Y
Haller
U
U
DiSaia
P J
PJ
Berns
M W
MW
D000622:Aminolevulinic Acid / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D005453:Fluorescence; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary*; D017319:Photosensitizing Agents / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX