Saihkay Hom N S, Rickards Karen J, Page Clive P, Ballinger James R
The Sackler Institute of Pulmonary Pharmacology, Waterloo Campus, King's College London, London SE1 9NH, UK.
J Pharmacol Toxicol Methods. 2011 Jan-Feb;63(1):69-78. doi: 10.1016/j.vascn.2010.05.001. Epub 2010 May 26.
Recent in vitro studies in our laboratory have demonstrated that platelets are necessary for leukocyte recruitment and airway remodelling in models of allergic airway inflammation, and also migrate to lung tissues in response to anti-IgE or relevant allergens in allergic asthma. Non-invasive imaging of platelet migration in vivo would provide a further insight into the roles of platelets in inflammatory diseases such as asthma, and metaiodobenzylguanidine (MIBG) was considered as a suitable platelet marker.
The kinetics of MIBG uptake into rabbit platelets, the effect of MIBG on platelet function and the effect of platelet activation on MIBG uptake and retention were investigated. MIBG-labelled platelets were administered intravenously into rabbits and the time course of radioactivity in the lung and blood was monitored as a function of stimulation.
Following a 4h incubation of MIBG in rabbit PRP, a near maximal MIBG uptake (52.4 ± 20.2%) in platelets occurred. This time point was chosen for subsequent in vitro studies. In vitro platelet function studies showed that MIBG has no effect on ADP or PAF-induced platelet aggregation, PAF-induced thromboxane production or fMLP-induced platelet chemotaxis. However, serotonin showed a significant effect on MIBG uptake and retention, but only at high concentrations. Stimulation of rabbit platelets with ADP and PAF caused a significant release of stored MIBG in vitro. Following i.v. administration of MIBG labelled platelets, the response to i.v. ADP and PAF stimulation was small but significant.
The release of MIBG from platelets in vivo, particularly following stimulation, leads to high background levels. Therefore, MIBG may have limited utility as a label for imaging platelets in vivo using PET. However, it may be a useful marker in detecting pathological conditions where platelet migration is involved.
我们实验室最近的体外研究表明，在过敏性气道炎症模型中，血小板对于白细胞募集和气道重塑是必需的，并且在过敏性哮喘中，血小板也会响应抗IgE或相关过敏原迁移至肺组织。体内血小板迁移的无创成像将进一步深入了解血小板在哮喘等炎症性疾病中的作用，而间碘苄胍（MIBG）被认为是一种合适的血小板标记物。
研究了MIBG摄取到兔血小板中的动力学、MIBG对血小板功能的影响以及血小板活化对MIBG摄取和保留的影响。将MIBG标记的血小板静脉注射到兔体内，并监测肺和血液中放射性的时间进程作为刺激的函数。
MIBG在兔富血小板血浆中孵育4小时后，血小板中出现了接近最大的MIBG摄取（52.4±20.2%）。该时间点被选用于后续的体外研究。体外血小板功能研究表明，MIBG对ADP或PAF诱导的血小板聚集、PAF诱导的血栓素产生或fMLP诱导的血小板趋化性没有影响。然而，血清素仅在高浓度时对MIBG摄取和保留有显著影响。用ADP和PAF刺激兔血小板会导致体外储存的MIBG显著释放。静脉注射MIBG标记的血小板后，对静脉注射ADP和PAF刺激的反应虽小但显著。
MIBG在体内从血小板中的释放，尤其是在刺激后，会导致高背景水平。因此，MIBG作为使用PET对体内血小板进行成像的标记物可能效用有限。然而，它可能是检测涉及血小板迁移的病理状况的有用标记物。
