Zober Tamas G, Mathews William B, Seckin Esen, Yoo Sung-Eun, Hilton John, Xia Jinsong, Sandberg Kathryn, Ravert Hayden T, Dannals Robert F, Szabo Zsolt
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817, USA.
Nucl Med Biol. 2006 Jan;33(1):5-13. doi: 10.1016/j.nucmedbio.2005.08.005.
The goal of this study was to investigate the binding characteristics of [(11)C]KR31173 and its applicability for PET studies of the AT(1) receptor (AT(1)R).
Ex vivo biodistribution and pharmacology were tested in mice. PET imaging was performed in mice, beagle dogs and a baboon. To assess nonspecific binding, PET imaging was performed both before and after pretreatment with a potent AT(1)R antagonist. In the baboon, PET imaging was also performed with the previously developed radioligand [(11)C]L-159,884 for comparison.
Ex vivo biodistribution studies in mice showed specific binding rates of 80-90% in the adrenals, kidneys, lungs and heart. Specific binding was confirmed in mice using small animal PET. In dogs, renal cortex tissue concentration at 75-95 min postinjection (pi) was 63 nCi/ml per millicurie at a specific binding rate of 95%. In the baboon renal cortex, tissue activity at 55-75 min pi was 345 nCi/ml per millicurie. In the baboon the specific binding of [(11)C]KR31173 was higher (81%) than the specific binding of [(11)C]L-159,884 (34%).
[(11)C]KR31173 shows accumulation and significant specific binding to the AT(1)R in the kidneys of mice, dogs and baboon. These findings suggest that this radioligand is suited for imaging the renal cortical AT(1)R in multiple species.
本研究旨在探究[(11)C]KR31173的结合特性及其在血管紧张素Ⅱ1型受体（AT(1)R）正电子发射断层显像（PET）研究中的适用性。
在小鼠体内进行了离体生物分布和药理学测试。对小鼠、比格犬和一只狒狒进行了PET成像。为评估非特异性结合，在给予强效AT(1)R拮抗剂预处理前后均进行了PET成像。在狒狒身上，还使用先前开发的放射性配体[(11)C]L-159,884进行PET成像以作比较。
小鼠的离体生物分布研究显示，肾上腺、肾脏、肺和心脏的特异性结合率为80% - 90%。使用小动物PET在小鼠体内证实了特异性结合。在犬类中，注射后75 - 95分钟时肾皮质组织浓度为每毫居里63纳居里/毫升，特异性结合率为95%。在狒狒的肾皮质中，注射后55 - 75分钟时组织活性为每毫居里345纳居里/毫升。在狒狒体内，[(11)C]KR31173的特异性结合（81%）高于[(11)C]L-159,884的特异性结合（34%）。
[(11)C]KR31173在小鼠、犬类和狒狒的肾脏中显示出对AT(1)R的积聚和显著特异性结合。这些发现表明，这种放射性配体适用于对多个物种的肾皮质AT(1)R进行成像。
