Christian Nicolas, Bol Anne, De Bast Marc, Labar Daniel, Lee John, Mahy Pierre, Grégoire Vincent
Center for Molecular Imaging and Experimental Radiotherapy, Université Catholique de Louvain, Av Hippocrate, 10, Brussels, 1200, Brussels, Belgium.
Eur J Nucl Med Mol Imaging. 2007 Sep;34(9):1348-54. doi: 10.1007/s00259-007-0376-7. Epub 2007 Mar 3.
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).
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.
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.
Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation.
2-(2-硝基咪唑-1-基)-N-(3,3,3-三氟丙基)乙酰胺(EF3)是一种2-硝基咪唑衍生物，在缺氧条件下会发生生物还原激活。在小鼠中使用PET示踪剂[18F]EF3时，观察到肿瘤与肌肉的比值在1.3至3.5之间。本研究调查了各种干预措施的影响，这些干预措施旨在通过提高肾滤过率（螺内酯、呋塞米）、减少肾小管重吸收（甲硝唑、奥硝唑、氨基酸溶液）或刺激胃肠道排泄（苯巴比妥）来增加[18F]EF3的消除，从而可能提高小鼠的肿瘤与本底噪声比值。
给C3H小鼠静脉注射平均12.95 MBq的[18F]EF3。在注射示踪剂前15分钟或实验前4天每天静脉注射药物（苯巴比妥）。使用专用动物PET（Mosaic，飞利浦）对麻醉后的小鼠在30至300分钟内进行成像。在肿瘤、膀胱、心脏、肝脏和腿部肌肉周围划定感兴趣区域。放射性以每克组织注射活性的百分比表示。
奥硝唑减少了[18F]EF3的尿排泄并增加了肝脏摄取，但其他器官未发生任何变化。苯巴比妥显著增加了肝脏浓度，降低了血液和肌肉中的放射性，而不影响肿瘤对示踪剂的摄取。因此，观察到肿瘤与本底噪声比值有小幅但不显著的增加。虽然其他药物也观察到了一些效果，但它们并未改变肿瘤与本底噪声比值。
只有苯巴比妥诱导了肿瘤与本底噪声比值增加的趋势，这可能在临床情况下进行测试。
