Virally-directed fluorescent imaging (VFI) can facilitate endoscopic staging.
BACKGROUND
Replication-competent, tumor specific herpes simplex virus NV1066 expresses green fluorescent protein (GFP) in infected cancer cells. We sought to determine the feasibility of GFP-guided imaging technology in the intraoperative detection of small tumor nodules.


METHODS
Human cancer cell lines were infected with NV1066 at multiplicities of infection of 0.01, 0.1 and 1. Cancer cell specific infectivity, vector spread and GFP signal intensity were measured by flow cytometry and time-lapse digital imaging (in vitro); and by use of a stereomicroscope and endoscope equipped with a fluorescent filter (in vivo).


RESULTS
NV1066 infected all cancer cell lines and expressed GFP at all MOIs. GFP signal was significantly higher than the autofluorescence of normal cells. One single dose of NV1066 spread within and across body cavities and selectively infected tumor nodules sparing normal tissue. Tumor nodules undetectable by conventional thoracoscopy and laparoscopy were identified by GFP fluorescence.


CONCLUSIONS
Virally-directed fluorescent imaging (VFI) is a real-time novel molecular imaging technology that has the potential to enhance the intraoperative detection of endoluminal or endocavitary tumor nodules.
Adusumilli
P S
PS
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Eisenberg
D P
DP
Stiles
B M
BM
Hendershott
K J
KJ
Stanziale
S F
SF
Chan
M-K
MK
Hezel
M
M
Huq
R
R
Rusch
V W
VW
Fong
Y
Y
D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D045744:Cell Line, Tumor; D004724:Endoscopy; D005240:Feasibility Studies; D005434:Flow Cytometry; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D006561:Herpes Simplex / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D049408:Luminescent Agents / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009367:Neoplasm Staging / Q000379:methods; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000821:virology*; D050504:Oncolytic Viruses / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000473:pathology; D010997:Pleural Neoplasms / Q000378:metabolism / Q000473:pathology; D018139:Simplexvirus / Q000378:metabolism*; D013997:Time Factors; D014779:Virus Replication
D049408:Luminescent Agents; D049452:Green Fluorescent Proteins