Rokka Johanna, Federico Cesare, Jurttila Jori, Snellman Anniina, Haaparanta Merja, Rinne Juha O, Solin Olof
Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Porthaninkatu 3, FI-20500, Turku, Finland.
J Labelled Comp Radiopharm. 2013 Jun 30;56(8):385-91. doi: 10.1002/jlcr.3055. Epub 2013 Jun 5.
(19)F/(18)F isotope exchange is a useful method to label drug molecules containing (19)F-fluorine with (18)F without modifying the drug molecule itself. Sphingosine-1-phosphate (S1P) is an important cellular mediator that functions by signaling through cell surface receptors. S1P is involved in several cell responses and may be related to many central nervous system disorders, including neural malfunction in Alzheimer's disease. In this study, [(18)F]1-benzyl-N-(3,4-difluorobenzyl)-2-isopropyl-6-(2-methoxyethoxy)-1H-indole-3-carboxamide, a novel (18)F-labeled positron emission tomography tracer for the S1P3 receptor, was successfully synthesized using the (19)F/(18)F isotope exchange reaction. Parameters of the reaction kinetics were studied, and correlations between the initial (18)F-activity, the amount of precursor, radiochemical yield and specific activity (SA) were determined. Contrary to expectations, high initial (18)F-activity decreased the radiochemical yield, and only a minor increase of SA occurred. This is most probably due to the complexity of the molecule and the subsequent susceptibility to radiolytic bond disruption. On the basis of the present results, a convenient condition for the (19)F/(18)F exchange reaction is the use of 2 µmol precursor with 20 GBq of (18)F-activity. This afforded a radiochemical yield of ~10% with an SA of 0.3 GBq/µmol. Results from this study are of interest for new tracer development where high initial (18)F-activity and (19)F/(18)F isotope exchange is used.
（19）F/（18）F同位素交换是一种有用的方法，可在不改变药物分子本身的情况下，用（18）F标记含（19）F-氟的药物分子。鞘氨醇-1-磷酸（S1P）是一种重要的细胞介质，通过细胞表面受体发出信号发挥作用。S1P参与多种细胞反应，可能与许多中枢神经系统疾病有关，包括阿尔茨海默病中的神经功能障碍。在本研究中，使用（19）F/（18）F同位素交换反应成功合成了一种新型的用于S1P3受体的（18）F标记正电子发射断层显像剂[（18）F]1-苄基-N-（3,4-二氟苄基）-2-异丙基-6-（2-甲氧基乙氧基）-1H-吲哚-3-甲酰胺。研究了反应动力学参数，并确定了初始（18）F活度、前体用量、放射化学产率和比活度（SA）之间的相关性。与预期相反，高初始（18）F活度降低了放射化学产率，且SA仅略有增加。这很可能是由于分子的复杂性以及随后对辐射分解键断裂的敏感性。基于目前的结果，（19）F/（18）F交换反应的一个便利条件是使用2µmol前体和20GBq的（18）F活度。这提供了约10%的放射化学产率，SA为0.3GBq/µmol。本研究结果对于使用高初始（18）F活度和（19）F/（18）F同位素交换的新型示踪剂开发具有重要意义。
