Institute of Biostructures and Bioimages of National Council of Research, Naples, Italy;
CEINGE scarl, Naples, Italy
References: Not available.
Animal Care in a Mouse Model of Amyotrophic Lateral Sclerosis Studied with [18F]DPA-714 Micro-PET/CT
SOD1G93A mice are a transgenic model of Amyotrophic lateral
sclerosis (ALS) to investigate in vivo neuroinflammation with innovative
translocator protein radioligands and positron emission
tomography (PET). The possibility to perform serial studies in the
same animal, from the asymptomatic to the advanced stages, is
highly desirable. Alterations of nutrition, hydration and of cardiovascular
hemodynamics provide challenges for researchers and
can adversely affect imaging studies. 10 hemyzigous SOD1G93A
mice (aged 71-137 days) were evaluated at different clinical stages
(CS, score range: 0-4) by [18F]DPA-714 PET/CT (GE Healthcare
eXplore Vista, resolution: 1.8 mm FWHM/200 μm). 5 mice were
longitudinally monitored. Weight, body condition (BCS, 0-5) and
dehydration were daily monitored. From CS and BCS scored as 2,
palatable source of hydration and energy were left on cage floor.
Glucose 5% /Ringer lactate or NaCl 0.9% solutions (1-3 ml/day)
with multivitaminic supplement were provided parenterally.
Mice were housed in dry cage with soft bed, avoiding social
isolation. Ocular discharges and ulcerative lesions were cleaned
(NaCl 0.9%; iodopovidone). Imaging studies were performed
under inhalant anesthesia (isoflurane 2% and oxygen 2 L/min).
Radiotracer uptake (SUV) was measured on PET/CT fusion images
in the cerebellum, brainstem, spinal cord normalized to those
of the frontal cortex using Osirix software. In the single PET/CT
group, 3 mice died after imaging study (CS: 1-2; BCS 3; weight
gain +2.87g), while 2 mice were euthanized after 6 days (CS: 4;
BCS 2; weight loss -3.04g). Mice performed from 2 to 5 imaging
sessions, with a mean survival of 6 days after the last PET/CT
(CS: 2-4; BCS 2-3; weight loss -1.68g). SUV showed an increased
trend overtime in brainstem compared to age-matched controls.
These findings underlie the relevant role played by the special
care of transgenic murine models in order to improve longitudinal
studies and minimize confounding variables.
The research leading to these results has received funding from the
European Union’s Seventh Framework Programme (FP7/2007-2013)
under grant agreement n° HEALTH-F2-2011-278850 (INMiND).
Animal Care in a Mouse Model of Amyotrophic Lateral Sclerosis Studied with [18F]DPA-714 Micro-PET/CT