Assessment of a chemically induced model of lung squamous cell carcinoma in mice by 18F-FDG small-animal PET.
BACKGROUND
Small-animal imaging has become a relevant research field in pre-clinical oncology. In particular, metabolic information provided by small-animal positron emission tomography (PET) is very useful to closely monitor tumour growth and assess therapy response in murine models of human disease. There are various murine models for human lung adenocarcinoma, but those for squamous cell lung carcinoma, the most common form of human cancer, are lacking.


OBJECTIVE
To assess the feasibility of 18F-FDG small-animal PET to monitor tumour growth in a chemically induced model of squamous cell carcinoma of the lung.


METHODS
Nineteen NIH Swiss mice were skin painted by N-nitroso-tris-chloroethylurea (NTCU) twice a week, with a 3 day interval, for 8 months and 10 NIH Swiss mice skin painted with NTCU solvent (acetone) were used as controls. 18F-FDG PET was performed under sevofluorane anaesthesia and oxygen supplementation at 2, 4, 6 and 8 months from initial treatment. Images were assessed by visual analysis and semi-quantitatively. When a diffuse distribution of tumour was noted, the mean of the counts/pixel measured at three lung levels, corrected for the effective dose injected and for decay, was used for comparison between mutagen-painted and control mice. Pathological evaluation was carried out from the time of the first positive PET results in a subgroup of the whole population to assess correlation with PET findings. Small animal CT was performed at 8 months in another subgroup.


RESULTS
In both terms of visual analysis and measurement of total lung activity, 18F-FDG PET at 2 and 4 months from initial treatment were comparable in mutagen-painted and controls. At 6 months, PET images showed a faint and diffuse uptake over both lung fields in mutagen-painted mice with multiple focal areas of increased tracer uptake that merged into confluent masses at 8 months and seriously subverting lung architecture on computed tomography. Total lung activity was significantly higher in mutagen-painted versus control mice at 6 (P=0.00000668) and 8 months (P=0.00000043) from initial treatment and paralleled the progressive lung involvement and histological severity.


CONCLUSIONS
18F-FDG PET may be useful in the assessment of this chemically induced murine model of lung squamous cells carcinoma. The total lung activity may be used as a measure of tumour metabolic activity of the tumour-bearing animals and may be useful in new drug testing studies.
Ambrosini
Valentina
V
Nuclear Medicine Department, Policlinico S. Orsola-Malpighi, Bologna University, Italy.
Nanni
Cristina
C
Pettinato
Cinzia
C
Fini
Milena
M
D'Errico
Antonia
A
Trepidi
Silvia
S
Spinelli
Antonello
A
Al-Nahhas
Adil
A
Rubello
Domenico
D
Zompatori
Maurizio
M
Fabbri
Mario
M
Franchi
Roberto
R
Fanti
Stefano
S
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D008175:Lung Neoplasms / Q000139:chemically induced / Q000000981:diagnostic imaging*; D051379:Mice; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18