Optical imaging of tumor cells in hollow fibers: evaluation of the antitumor activities of anticancer drugs and target validation.
The in vivo hollow fiber assay, in which semipermeable hollow fibers filled with tumor cells, are implanted into animals, was originally developed to screen for anticancer compounds before assessment in more complex tumor models. To enhance screening and evaluation of anticancer drugs, we have applied optical imaging technology to this assay. To demonstrate that tumor cells inside hollow fibers can communicate with the host mice, we have used fluorescence imaging in vivo and CD31 immunostaining ex vivo to show that angiogenesis occurs around cell-filled hollow fibers by 2 weeks after subcutaneous implantation. Bioluminescence imaging has been used to follow the number of luciferase-expressing tumor cells within implanted hollow fibers; proliferation of those cells was found to be significantly inhibited by docetaxel or irinotecan. We also used bioluminescence imaging of hollow fibers to monitor the nuclear factor kappaB (NFkappaB) pathway in vivo; NFkappaB activation by lipopolysaccharide and tumor necrosis factor-alpha was evaluated in tumor cell lines genetically engineered to express luciferase controlled by an NFkappaB-responsive element. These results demonstrate that optical imaging of hollow fibers containing reporter tumor cells can be used for the rapid and accurate evaluation of antitumor activities of anticancer drugs and for measurement of molecular pathways.
Zhang
Guo-Jun
GJ
Imaging Department, MRL, Merck and Co., Inc., West Point, PA 19486, USA. guo_jun_zhang@merck.com
Chen
Tsing-Bau
TB
Bednar
Bohumil
B
Connolly
Brett M
BM
Hargreaves
Richard
R
Sur
Cyrille
C
Williams
David L
DL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000032:analysis; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000295:instrumentation / Q000379:methods; D055095:Optics and Photonics; D051381:Rats; D014407:Tumor Cells, Cultured