Edwards David, Jones Paul, Haramis Helena, Battle Mark, Lear Rochelle, Barnett D Jon, Edwards Catherine, Crawford Hazel, Black Andrew, Godden Vanessa
Research and Development, GE Healthcare, Medical Diagnostics, The Grove Centre, HP7 9LL Amersham, UK.
Nucl Med Biol. 2008 Apr;35(3):365-75. doi: 10.1016/j.nucmedbio.2007.11.010.
Technetium 99m (99mTc)-NC100692 is being developed as a marker of vitronectin receptor expression. The purpose of this study was to confirm the binding affinity [dissociation constant (Kd)] of 99mTc-NC100692 for a range of integrin receptors including alphavbeta3 and alphavbeta5 as well as to establish the biodistribution and metabolic stability of 99mTc-NC100692 in Wistar rats.
The Kd of 99mTc-NC100692 for a range of human integrin receptors was established in an in vitro saturation binding assay. The biodistribution and metabolic stability of 99mTc-NC100692 in normal Wistar rats was investigated.
The Kd of 99mTc-NC100692 to alphavbeta3 and alphavbeta5 was less than 1 nM. It was not possible to saturate the binding of 99mTc-NC10092 towards alphaIIbbeta3, alpha5beta1, alpha3beta1 or alpha1beta1, and as a result, accurate Kd values could not be determined. The biodistribution of 99mTc-NC100692 in male and female Wistar rats showed that radioactivity was rapidly excreted, predominantly into the urine, with very little background tissue retention apart from the liver and kidneys. Kidney and liver retention was reduced in the presence of excess NC100692 ligand. In vivo, there was little systemic metabolism of 99mTc-NC100692.
99mTc-NC100692 has a high affinity for the vitronectin receptors that are associated with angiogenesis. 99mTc-NC100692 is metabolically stable in the systemic circulation of rats with a biodistribution that is favourable for imaging purposes. This evidence suggests that 99mTc-NC100692 might be a useful marker of vitronectin receptor expression in vivo.
锝99m（99mTc）-NC100692正被开发作为玻连蛋白受体表达的标志物。本研究的目的是确认99mTc-NC100692对包括αvβ3和αvβ5在内的一系列整合素受体的结合亲和力[解离常数（Kd）]，并确定99mTc-NC100692在Wistar大鼠体内的生物分布和代谢稳定性。
通过体外饱和结合试验确定99mTc-NC100692对一系列人整合素受体的Kd。研究99mTc-NC100692在正常Wistar大鼠体内的生物分布和代谢稳定性。
99mTc-NC100692对αvβ3和αvβ5的Kd小于1 nM。99mTc-NC10092与αIIbβ3、α5β1、α3β1或α1β1的结合无法饱和，因此无法确定准确的Kd值。99mTc-NC100692在雄性和雌性Wistar大鼠体内的生物分布表明，放射性物质迅速排出，主要进入尿液，除肝脏和肾脏外，背景组织保留极少。在过量NC100692配体存在的情况下，肾脏和肝脏的保留减少。在体内，99mTc-NC100692几乎没有全身代谢。
99mTc-NC100692对与血管生成相关的玻连蛋白受体具有高亲和力。99mTc-NC100692在大鼠体循环中代谢稳定，其生物分布有利于成像。这一证据表明，99mTc-NC100692可能是体内玻连蛋白受体表达的有用标志物。
