Delforge Jacques, Mesangeau Didier, Dolle Frédéric, Merlet Pascal, Loc'h Christian, Bottlaender Michel, Trebossen Régine, Syrota André
Service Hospitalier Frédéric Joliot, Commissariat à l'Energie Atomique/Direction des Sciences du Vivant, Orsay, France.
J Nucl Med. 2002 Feb;43(2):215-26.
Previous studies showed that the in vivo concentration of beta-adrenergic receptor sites can be estimated by PET using (-)-4-((S)-3-tert-butylamino-2-hydroxypropoxy)-1,3-dihydrobenzoimidazol-2-one (CGP 12177), a hydrophilic ligand. A graphic method was previously proposed and used by several groups. However, this approach was not completely validated. The purpose of this study was to improve and confirm the validity of this approach through a better knowledge of the associated ligand-receptor model, estimated for the first time using the multiinjection approach.
The concentration of beta-adrenergic receptor sites was estimated for mini pigs using 2 methods. The first was the usual multiinjection approach, which permits estimation of all model parameters, including receptor concentration. However, this approach needs a complex protocol, including blood sampling, thereby making it difficult to use for studies on patients. The second method was the CGP 12177 graphic method. This approach permits the estimation of only receptor concentration but has the advantage of not requiring blood sampling. Another advantage is the ability to generate parametric images easily.
Using the multiinjection approach, we obtained for the first time a complete model describing interactions between CGP 12177 and beta-adrenergic receptors. Knowledge of all parameters of this model permitted good validation of the assumptions included in the graphic method. The concentration of beta-adrenergic receptor sites in mini pigs was estimated at 15.2 +/- 3.4 pmol/mL.
The graphic method has been improved by taking into account various phenomena, such as protein binding and the nonlinearity between plasma concentration and injected dose. This method is now usable for patient studies and offers the ability to estimate the beta-adrenergic receptor concentration from a single PET experiment without blood sampling. Parametric imaging will enable screening of the receptor site location and observation of potential anomalies in patients.
先前的研究表明，使用亲水性配体（-）-4-（（S）-3-叔丁基氨基-2-羟基丙氧基）-1,3-二氢苯并咪唑-2-酮（CGP 12177）通过正电子发射断层扫描（PET）可以估计体内β-肾上腺素能受体位点的浓度。先前曾有几个研究小组提出并使用了一种图解法。然而，这种方法并未得到完全验证。本研究的目的是通过更好地了解相关的配体-受体模型来改进并确认这种方法的有效性，该模型首次使用多次注射法进行估计。
使用两种方法估计小型猪体内β-肾上腺素能受体位点的浓度。第一种是常用的多次注射法，它可以估计所有模型参数，包括受体浓度。然而，这种方法需要一个复杂的方案，包括采血，因此难以用于患者研究。第二种方法是CGP 12177图解法。这种方法仅能估计受体浓度，但优点是不需要采血。另一个优点是能够轻松生成参数图像。
使用多次注射法，我们首次获得了一个完整的模型，该模型描述了CGP 12177与β-肾上腺素能受体之间的相互作用。了解该模型的所有参数有助于很好地验证图解法中包含的假设。小型猪体内β-肾上腺素能受体位点的浓度估计为15.2±3.4 pmol/mL。
通过考虑各种现象，如蛋白质结合以及血浆浓度与注射剂量之间的非线性关系，图解法得到了改进。这种方法现在可用于患者研究，并且能够在不采血的情况下通过单次PET实验估计β-肾上腺素能受体浓度。参数成像将能够筛查受体位点位置并观察患者潜在的异常情况。
