Baranwal Aparna, Patel Himika H, Mukherjee Jogeshwar
Preclinical Imaging, Department of Radiological Sciences, University of California - Irvine, Irvine, CA, 92697, USA.
J Labelled Comp Radiopharm. 2014 Feb;57(2):86-91. doi: 10.1002/jlcr.3168. Epub 2013 Dec 11.
The Maillard reaction of sugars and amines resulting in the formation of glycosylamines and Amadori products is of biological significance, for drug delivery, role in central nervous system, and other potential applications. We have examined the interaction of (18) F-fluorodeoxyglucose ((18) F-FDG) with biological amines to study the formation of (18) F-fluorodeoxyglycosylamines ((18) F-FDGly). Respective amines N-allyl-2-aminomethylpyrrolidine (NAP) and 2-(4'-aminophenyl)-6-hydroxybenzothiazole (PIB precursor) were mixed with FDG to provide glycosylamines, FDGNAP and FDGBTA. Radiosynthesis using (18) F-FDG (2-5 mCi) was carried out to provide (18) F-FDGNAP and (18) F-FDGBTA. Binding of FDGBTA and (18) F-FDGBTA was evaluated in human brain sections of Alzheimer's disease (AD) patients and control subjects using autoradiography. Both FDGNAP and FDGBTA were isolated as stable products. Kinetics of (18) F-FDGNAP reaction indicated a significant product at 4 h (63% radiochemical yield). (18) F-FDGBTA was prepared in 57% yield. Preliminary studies of FDGBTA showed displacement of (3) H-PIB (reduced by 80%), and (18) F-FDGBTA indicated selective binding to Aβ-amyloid plaques present in postmortem AD human brain, with a gray matter ratio of 3 between the AD patients and control subjects. We have demonstrated that (18) F-FDG couples with amines under mild conditions to form (18) F-FDGly in a manner similar to click chemistry. Although these amine derivatives are stable in vitro, stability in vivo and selective binding is under investigation.
糖与胺发生美拉德反应生成糖基胺和阿马多里产物，这在药物递送、中枢神经系统作用及其他潜在应用方面具有生物学意义。我们研究了（18）F-氟脱氧葡萄糖（（18）F-FDG）与生物胺的相互作用，以研究（18）F-氟脱氧糖基胺（（18）F-FDGly）的形成。将各自的胺N-烯丙基-2-氨基甲基吡咯烷（NAP）和2-（4'-氨基苯基）-6-羟基苯并噻唑（PIB前体）与FDG混合以提供糖基胺FDGNAP和FDGBTA。使用（18）F-FDG（2-5毫居里）进行放射性合成以得到（18）F-FDGNAP和（18）F-FDGBTA。使用放射自显影术在阿尔茨海默病（AD）患者和对照受试者的人脑切片中评估FDGBTA和（18）F-FDGBTA的结合。FDGNAP和FDGBTA均作为稳定产物被分离出来。（18）F-FDGNAP反应的动力学表明在4小时时有显著产物（放射化学产率为63%）。（18）F-FDGBTA的制备产率为57%。对FDGBTA的初步研究表明（3）H-PIB的置换（降低了80%），并且（18）F-FDGBTA表明其选择性结合于死后AD人脑内存在的Aβ-淀粉样斑块，AD患者与对照受试者之间的灰质比率为3。我们已经证明（18）F-FDG在温和条件下与胺偶联以类似于点击化学的方式形成（18）F-FDGly。尽管这些胺衍生物在体外是稳定的，但它们在体内的稳定性和选择性结合正在研究中。
