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 intervention.


METHODS
Human ovarian tumor cells (SKOV3.ip1) were infected with a replication-deficient adenoviral (Ad) vector encoding green fluorescent protein (GFP). The GFP-positive tumor cells were imaged in vitro and in vivo with a fluorescence stereomicroscope. Using appropriate filters, both GFP fluorescence and adriamycin were simultaneously detected. Nude mice implanted with GFP-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 fluorescence was confirmed to be dead cells. For in vivo imaging, intraperitoneal tumors as small as 0.2 mm in diameter were detected externally. Adriamycin uptake was detected in tumors by in vivo imaging, and reduction in tumor size was concurrent with decrease in GFP fluorescence. These findings were confirmed at necropsy.


CONCLUSIONS
Fluorescence stereomicroscopy monitored the response of ovarian xenografts to adriamycin therapy. For the first time, GFP and adriamycin were imaged simultaneously.
Chaudhuri
T R
TR
Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. DrTRC@uab.edu
Mountz
J M
JM
Rogers
B E
BE
Partridge
E E
EE
Zinn
K R
KR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008991:Monitoring, Physiologic / Q000379:methods; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D004317:Doxorubicin