Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model.
OBJECTIVE
The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [18F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [18F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital).


METHODS
C3H mice were injected i.v. with an average of 12.95 MBq of [18F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue.


RESULTS
Ornidazole decreased the urinary excretion and increased the liver uptake of [18F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio.


CONCLUSIONS
Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation.
Christian
Nicolas
N
Center for Molecular Imaging and Experimental Radiotherapy, Université Catholique de Louvain, Av Hippocrate, 10, Brussels, 1200, Brussels, Belgium. nicolas.christian@imre.ucl.ac.be
Bol
Anne
A
De Bast
Marc
M
Labar
Daniel
D
Lee
John
J
Mahy
Pierre
P
Grégoire
Vincent
V
D000818:Animals; D019540:Area Under Curve; D000860:Hypoxia; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D009950:Ornidazole / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D013148:Spironolactone / Q000494:pharmacology; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome
C438056:2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)-acetamide; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; D013148:Spironolactone; D009950:Ornidazole