Monitoring with a non-invasive bioluminescent in vivo imaging system of pleural metastasis of lung carcinoma.
OBJECTIVE
The prognosis of patients with malignant pleural effusion (MPE) is poor. An MPE model is necessary for developing new therapeutic strategies. We established a MPE model and investigated the therapeutic effects of the administration of serial doses of docetaxel on intrathoracic disseminated foci using an in vivo image system (IVIS).


METHODS
First, mice without pleural metastasis of lung carcinoma were given a single injection of docetaxel (Taxotere) in the thoracic cavity. The average weight of each group was evaluated. Next, docetaxel was injected into the thoracic cavity of the mice once a week for 8 weeks. Again, the average weight of each group was evaluated. Finally, A549 lung cancer cells transfected with luciferase gene (A549-Luc) were injected into the intrapleural cavity of the mouse. When pleural metastasis was established, we started repeated intrapleural administration of docetaxel (once a week for 8 weeks). The average weight of each group and the survival period was evaluated. All bioluminescent data were collected and analysed with a Xenogen IVIS system.


RESULTS
(1) Single administration study: The average weight of mice injected with 50mg/kg docetaxel dropped 10%. (2) Repeat administration study: In the group of mice injected with 25mg/kg or 50mg/kg docetaxel, the average weight dropped by 10%. (3) A549-Luc cells were injected into the thoracic cavity of the mice. Autopsies revealed disseminated foci in thoracic cavity 7 days or more after inoculation. After confirmation of tumor formation, repeated injections of docetaxel were administered. After 21 days, photon counts from the thoracic cavity of untreated mice increased. Repeated intrapleural administration of docetaxel prolonged survival when compared to the control group.


CONCLUSIONS
(1) We established a MPE model. (2) IVIS facilitates faster and more accurate counting of disseminated foci in the pleura (as compared to the previous standard of measuring body weight changes) in a cancerous pleuritis model. (3) Repeated intrapleural administration of docetaxel is effective.
Matsumoto
Seiji
S
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Tanaka
Fumihiro
F
Sato
Kiyoshi
K
Kimura
Shinya
S
Maekawa
Taira
T
Hasegawa
Seiki
S
Wada
Hiromi
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D000077143:Docetaxel; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007267:Injections; D049409:Luciferases, Firefly / Q000032:analysis / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016066:Pleural Effusion, Malignant / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D049409:Luciferases, Firefly