Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18 kDa) with PET
Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18 kDa) with PET
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DOI：
10.1002/jlcr.1523
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发表时间：
2008-06-01
影响因子：
1.8
通讯作者：
Dolle, Frederic
中科院分区：
文献类型：
--
作者：
Damont, Annelaure;Hinnen, Francoise;Dolle, Frederic
最近，一系列新的2-苯基吡唑[1,5-a]嘧啶乙酰胺被报道为转运蛋白（18 kDa）的选择性配体。在该系列中，DPA-714 （nn -二乙基-2-（2-（4-（2-氟乙氧基）苯基）-5,7-二甲基吡唑[1,5-a]嘧啶-3-基）乙酰胺，K(i)=7.0 nM）是一种化合物，其结构中设计有一个氟原子，可以用氟-18（半衰期：109.8分钟）进行标记，并使用正电子发射断层扫描进行体内成像。以DPA-713 （N，N-二乙基-2-（2-（2-甲苯磺酰基氧氧乙氧基）苯基）-5,7-二甲基吡唑[1,5-a]嘧啶-3-基）乙酰胺为前体，分两步合成了DPA-714及其tosyloxy衍生物(nn -二乙基-2-（2-（4-甲氧基苯基）-5,7-二甲基吡唑[1,5-a]嘧啶-3-基）乙酰胺，其产率分别为32%和42%。[(18)FIDPA-714的合成采用简单的一步法（tosyloxy-for-氟亲核脂肪族取代），该过程在Zymate-XP机器人系统上完全自动化。实验包括：(A) K[(18)F]F- kryptofix 222与tosyloxy前体（4.5-5.0 mg, 8.2-9.1 mu mol）在盐酸二甲基（0.2 ml）中165℃反应5 min，然后(B) C18 PrepSep药盒预纯化，最后(C)在Waters X-Terra(TM) RP18上进行半制备型高效液相色谱（HPLC）纯化。通常情况下，从37GBq [(18)F]氟化物批次（总体非衰变校正和分离放射化学产率：15-20%）开始，在85-90分钟内，可以获得5.6-7.4 GBq [(18)F]DPA-714（化学和放射化学纯度为95%），比放射性在37至111 GBq/ μ mol之间（包括HPLC纯化和SepPak (R)基配方）。
Recently, a novel series of 2-phenylpyrazolo[1,5-a]pyrimidineacetamides has been reported as selective ligands of the translocator protein (18 kDa). Within this series, DPA-714 (NN-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide, K(i)=7.0 nM) is a compound, which had been designed with a fluorine atom in its structure, allowing labelling with fluorine-18 (half-life: 109.8 min) and in vivo imaging using positron emission tomography. DPA-714 and its tosyloxy derivative (NN-diethyl-2-(2-(4-(2-toluenesulfonyloxyethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) as precursor for the labelling with fluorine-18 were synthesized in two steps from DPA-713 (N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) and obtained in 32 and 42% yields, respectively. [(18)FIDPA-714 was synthesized using a simple one-step process (a tosyloxy-for-fluorine nucleophilic aliphatic substitution), which has been fully automated on our Zymate-XP robotic system. It involves: (A) reaction of K[(18)F]F-Kryptofix 222 with the tosyloxy precursor (4.5-5.0 mg, 8.2-9.1 mu mol) at 165 degrees C for 5 min in dimethyl sufloxide (0.6ml.) followed by (B) C18 PrepSep cartridge pre-purification and finally (C) semi-preparative high-performance liquid chromatography (HPLC) purification on a Waters X-Terra(TM) RP18. Typically, 5.6-7.4 GBq of [(18)F]DPA-714 (> 95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111 GBq/mu mol within 85-90 min (HPLC purification and SepPak (R)-based formulation included), starting from a 37GBq [(18)F]fluoride batch (overall non-decay-corrected and isolated radiochemical yield: 15-20%).