A 99Tcm-labelled leukotriene B4 receptor antagonist for scintigraphic detection of infection in rabbits
A 99Tcm-labelled leukotriene B4 receptor antagonist for scintigraphic detection of infection in rabbits
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DOI：
10.1097/00006231-200011000-00010
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发表时间：
2000-11-01
影响因子：
1.5
通讯作者：
Corstens, FHM
中科院分区：
文献类型：
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作者：
Brouwers, AH;Laverman, P;Corstens, FHM
为了寻找一种快速、准确的显像剂用于感染和炎症的免疫显像检测，最近开发了一种LTB_4受体拮抗剂Tc-99（m）-RP_（517），它含有肼基烟酰胺部分。为了研究Tc-99（m）-RP 517的体内行为，对大肠杆菌感染的家兔静脉注射Tc-99（m）-RP 517。获得伽马照相机图像，并在注射后（p.i.）数小时测定离体生物分布。在另一组家兔中，对胆总管进行插管，以定量监测放射性药物的肝胆清除率。放射性标记的RP 517的受体结合分数超过70%。Tc-99（m）-RP 517在脓肿中的蓄积早在注射后1 h就可见。由于快速血液清除（t1/2 α =18 +/- 0.6 min，t1/2 β =6.5 +/- 0.4 h）和高脓肿摄取，脓肿-肌肉比随时间增加，从注射后1 h的7.0 +/- 2.3增加。至44.3 +/- 4.6（20 h p.i.）该药物主要通过肝胆途径清除：在注射后1小时，在小肠中回收了50%的放射性标记，而在感染后20小时，盲肠和乙状结肠中发现了85%。结论：Tc-99（m）-RP 517能快速显示大肠杆菌。兔大肠杆菌感染。该药物从血液中迅速清除，主要通过肝胆途径。实现了高的荧光背景比。在肠道中的积累可能会限制该试剂用于检测腹部区域感染过程的适用性。开发亲水性更强的Tc-99（m）-RP 517类似物可提高该药物的临床应用价值。((C)2000 Lippincott威廉姆斯和威尔金斯）。
In a search for a rapid and accurate imaging agent for scintigraphic detection of infection and inflammation, an LTB4 receptor antagonist, Tc-99(m)-RP517, which contains the hydrazino nicotinamide moiety, has been del eloped recently. To study the in vivo behaviour of Tc-99(m)-RP517, rabbits with Escherichia coli infection were injected intravenously with Tc-99(m)-RP517. Gamma camera images were obtained and ex vivo bio-distribution was determined at several hours post-injection (p.i.). In a separate set of rabbits the choledochal duct was cannulated to quantitatively monitor the hepatobiliary clearance of the radiopharmaceutical. The receptor binding fraction of the radiolabelled RP517 exceeded 70%. Accumulation of Tc-99(m)-RP517 in the abscess was visualized as early as Ih p.i. Due to rapid blood clearance (t1/2 alpha =18 +/- 0.6 min, t1/2 beta =6.5 +/- 0.4 h) and high abscess uptake, the abscess-to-muscle ratios increased with time from 7.0 +/- 2.3 at 1 h p.i. to 44.3 +/- 4.6 at 20 h p.i. The agent mainly cleared via the hepatobiliary route: 50% of the radiolabel was recovered in the small bowel at 1 h p.i., whereas 85% was found in cecum and sigmoid at 20 h p.i. In conclusion, Tc-99(m)-RP517 rapidly visualized E. coli abscesses in rabbits. The agent rapidly cleared from the blood, mainly via the hepatobiliary route. High abscess-to-background ratios were achieved. The accumulation in the intestines could limit the applicability of this agent for detecting infectious processes in the abdominal area. The development of a more hydrophilic analogue of Tc-99(m)-RP517 could improve the clinical applicability of this agent. ((C) 2000 Lippincott Williams & Wilkins).