Assessment of a chemically induced model of lung squamous... : Nuclear Medicine Communications (original) (raw)

ORIGINAL ARTICLES

Assessment of a chemically induced model of lung squamous cell carcinoma in mice by 18F-FDG small-animal PET

Ambrosini, Valentinaa b c; Nanni, Cristinaa; Pettinato, Cinziaa; Fini, Milenac; D'Errico, Antoniad; Trepidi, Silviaa; Spinelli, Antonelloa; Al-Nahhas, Adile; Rubello, Domenicof; Zompatori, Mauriziog; Fabbri, Marioc; Franchi, Robertoa; Fanti, Stefanoa

aNuclear Medicine Department, Policlinico S. Orsola-Malpighi

bSurgery Department, Istituto ‘A. Valsalva’

cPulmonary Department, Bologna University, Italy

dPathology Department, Istituto di Ricerca Codivilla-Putti, Istituti Ortopedici Rizzoli, Bologna, Italy

eDepartment of Nuclear Medicine, Hammersmith Hospital, London, UK

fNuclear Medicine Service, S. Maria della Misericordia Hospital, Rovigo, Italy

gRadiology Department, Parma University, Italy

Correspondence to Dr Adil AL-Nahhas, Department of Nuclear Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK

Tel: +44 208 383 4923; fax: +44 208 383 1700;

e-mail: [email protected]

Received 13 February 2007 Revised 29 March 2007 Accepted 16 April 2007

Abstract

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.

Aim

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.

Materials and 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.