Noninvasive of adenovirus tumor retargeting in living subjects by a soluble adenovirus receptor-epidermal growth factor (sCAR-EGF) fusion protein.
OBJECTIVE
To demonstrate that non-invasive bioluminescent imaging can monitor restricted expression from a nonreplicating adenovirus in which the cyclooxygenase-2 (COX-2) promoter drives firefly luciferase.


METHODS
Adenovirus in which the COX-2 promoter drives the firefly luciferase imaging gene was injected intratumorally into xenografts that express relatively low and relatively high levels of COX-2. Adenovirus that expresses Renilla Luciferase from the cytomegalovirus early promoter was co-injected, to normalize for injection, leakage, vascularization, etc. COX-2 restricted firefly luciferase and global Renilla Luciferase activities were measured by optical imaging techniques both in vivo and in isolated tissues.


RESULTS
Dramatic reduction in hepatic luciferase expression after intravenous viral injection can be imaged non-invasively in living animals. Following intratumoral injection, luciferase levels in tumor xenografts that express differing endogenous COX-2 levels reflect the luciferase levels observed when these cells are infected in cell culture. Essentially no luciferase expression is observed in liver following intratumoral injection.


CONCLUSIONS
Both tissue restricted expression and transcriptional redirection to tumors expressing COX-2 can be imaged non-invasively following injection of Adenovirus expressing firefly luciferase from the COX-2 promoter.
Liang
Qianwa
Q
Department of Biological Chemistry, Molecular Biology Institute, David Geffen School of Medicine, Los Angeles, CA USA.
Dmitriev
Igor
I
Kashentseva
Elena
E
Curiel
David T
DT
Herschman
Harvey R
HR
D000256:Adenoviridae / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism / Q000821:virology; D049409:Luciferases, Firefly / Q000032:analysis / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy / Q000821:virology; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D013270:Stomach / Q000821:virology; D014161:Transduction, Genetic
D008565:Membrane Proteins; D011991:Receptors, Virus; D011994:Recombinant Proteins; C085301:adenovirus receptor; D004815:Epidermal Growth Factor; D049409:Luciferases, Firefly; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors