Light-based imaging of green fluorescent protein-positive ovarian cancer xenografts during therapy

Objective. The purpose of the study was to develop a sensitive, noninvasive imaging method for monitoring ovarian xenografts during therapeutic interv ention. Methods. Human ovarian tumor cells (SKOV3.ip1) were infected with a replica tion-deficient adenoviral (Ad) vector encoding green fluorescent protein (G FP). The GFP-positive tumor cells were imaged in vitro and in vivo with a f luorescence stereomicroscope. Using appropriate filters, both GFP fluoresce nce and adriamycin were simultaneously detected. Nude mice implanted with G FP-positive cells were imaged repeatedly, in a noninvasive manner. Results. SKOV3.ip1 cells infected with Ad-GFP showed high GFP fluorescence, which was eliminated after treatment with adriamycin. Loss of GFP fluoresc ence was confirmed to be dead cells. For in vivo imaging, intraperitoneal t umors as small as 0.2 mm in diameter were detected externally. Adriamycin u ptake was detected in tumors by in vivo imaging, and reduction in tumor siz e was concurrent with decrease in GFP fluorescence. These findings were con firmed at necropsy. Conclusions. Fluorescence stereomicroscopy monitored the response of ovaria n xenografts to adriamycin therapy. For the first time, GFP and adriamycin were imaged simultaneously. (C) 2001 Academic Press.