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首页> 外文期刊>RSC Advances >Design, synthesis and preliminary evaluation of a novel SPECT DTPA-bis-triazaspirodecanone conjugate for D-2 receptor imaging
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Design, synthesis and preliminary evaluation of a novel SPECT DTPA-bis-triazaspirodecanone conjugate for D-2 receptor imaging

机译：D-2受体成像的新型SPECT DTPA-双-三氮杂螺烷酮共轭物的设计，合成和初步评估

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On the basis of pharmacological behaviour, dopamine receptors are divided into D-1 and D-2 subtype, which are primarily responsible for several neurophysiological anomalies. Assessment and validation with SPECT based conjugates provides a promising and cost effective insight to detect molecular changes in such neurological diseases. Spiperone, a well known "butryophenone" based D-2 receptor antagonist, has been explored to design a novel conjugate for SPECT evaluation. The molecular docking pose analysis of the designed molecule was explored with dopamine D-2 receptor. The molecule showed high affinity (-51.318 kcal mol(-1)) due to conserved interactions with Asp114 and Phe389 of D-2 receptor. DTPA with triazaspirodecanone moiety of spiperone was synthesized using bifunctional chelation approach with 88% yield and has been characterized using NMR and mass spectroscopy. The radiolabeling efficiency of Tc-99m-DTPA-bis-(1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one) was 98%. The complex showed appreciable brain uptake in mice. Receptor binding experiments revealed a K-d of 6.26 nM with maximum localization of the conjugate in the striatum. Thus, these studies could be viewed as novel and informative, initial proof-of-concept approach to the field of Tc-99m-labeled radioligand design.
机译：根据药理行为，将多巴胺受体分为D-1和D-2亚型，这主要是造成几种神经生理异常的原因。使用基于SPECT的结合物进行评估和验证，为检测此类神经疾病中的分子变化提供了有希望且具有成本效益的见解。已开发出基于已知的“丁苯酮”的D-2受体拮抗剂Spiperone，以设计用于SPECT评估的新型偶联物。用多巴胺D-2受体探索了设计分子的分子对接姿势分析。该分子显示出高亲和力（-51.318 kcal mol（-1））由于与D-2受体的Asp114和Phe389保守相互作用。使用双功能螯合法合成了具有哌啶的三氮杂螺并十二烷酮部分的DTPA，收率为88％，并已使用NMR和质谱进行了表征。 Tc-99m-DTPA-双-（1-苯基-1,3,8-三氮杂螺[4,5] decan-4-one）的放射标记效率为98％。该复合物在小鼠中显示出明显的脑摄取。受体结合实验表明，K-d为6.26 nM，结合物在纹状体中最大定位。因此，这些研究可被视为Tc-99m标记的放射性配体设计领域的新颖且内容丰富的初始概念验证方法。

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