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[18F]-labeled positron emission tomography ligand for the histamine H4 receptor
Journal of Labelled Compounds and Radiopharmaceuticals ( IF 0.9 ) Pub Date : 2021-06-05 , DOI: 10.1002/jlcr.3929 Agnieszka Zak 1 , Lucas Lemaire 1 , Sylvie Chalon 2 , Gabrielle Chicheri 2, 3 , Hamid Marzag 1 , Sylvie Bodard 2 , Sophie Sérrière 2 , Sylvain Routier 1 , Frédéric Buron 1 , Johnny Vercouillie 2, 3, 4
Journal of Labelled Compounds and Radiopharmaceuticals ( IF 0.9 ) Pub Date : 2021-06-05 , DOI: 10.1002/jlcr.3929 Agnieszka Zak 1 , Lucas Lemaire 1 , Sylvie Chalon 2 , Gabrielle Chicheri 2, 3 , Hamid Marzag 1 , Sylvie Bodard 2 , Sophie Sérrière 2 , Sylvain Routier 1 , Frédéric Buron 1 , Johnny Vercouillie 2, 3, 4
Affiliation
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We synthesized 5-[18F]-fluoro-1H-indol-2-yl)(4-methyl-1-piperazinyl)methanone ([18F]5) via a Suzuki approach starting from a protected pinacol borane precursor followed by acidic hydrolysis of the t-Boc protecting group. The non-optimized radiochemical yield was 5.7 ± 1.35%, radiochemical purity was over 99%, and molar activity was 100.7 ± 34.5 GBq/μmol (n = 3). [18F]5 was stable in rat plasma for at least 4 h and was evaluated by μPET imaging and biodistribution using a unilateral quinolinic acid rat model of neuroinflammation. The time-activity curve showed that [18F]5 entered the brain immediately after intravenous injection and then left it progressively with a very low level reached from 30 min after injection. The biodistribution study showed no difference in the accumulation of [18F]5 between the lesioned and intact side of the brain and between control rats and animals pretreated with a saturating dose of JNJ-7777120 as a specific H4R antagonist. Hence, despite its in vitro nanomolar affinity for H4R, and its ability to cross the blood–brain barrier in rats, [18F]5 does not appear suitable to image in vivo the receptor by PET.
中文翻译：
[18F] 标记的组胺 H4 受体正电子发射断层扫描配体
我们通过 Suzuki 方法合成了 5-[ 18 F]-氟-1 H-吲哚-2-基）（4-甲基-1-哌嗪基）甲酮（[ 18 F] 5 ），从受保护的频哪醇硼烷前体开始，然后t -Boc保护基团的酸性水解。未优化的放化收率为5.7±1.35%，放化纯度大于99%，摩尔活度为100.7±34.5 GBq/μmol（ n =3）。 [ 18 F] 5在大鼠血浆中稳定至少4小时，并使用单侧喹啉酸大鼠神经炎症模型通过μPET成像和生物分布进行评估。时间-活性曲线显示[ 18 F] 5静脉注射后立即进入大脑，然后逐渐离开大脑，注射后30分钟达到很低的水平。生物分布研究显示，大脑受损侧和完整侧之间以及对照大鼠和用饱和剂量的 JNJ-7777120 作为特异性 H4R 拮抗剂预处理的动物之间，[ 18 F] 5的积累没有差异。因此，尽管 [ 18 F] 5在体外对 H4R 具有纳摩尔亲和力，并且能够穿过大鼠的血脑屏障，但它似乎不适合通过 PET 对受体进行体内成像。
更新日期：2021-07-07
中文翻译：
[18F] 标记的组胺 H4 受体正电子发射断层扫描配体
我们通过 Suzuki 方法合成了 5-[ 18 F]-氟-1 H-吲哚-2-基）（4-甲基-1-哌嗪基）甲酮（[ 18 F] 5 ），从受保护的频哪醇硼烷前体开始，然后t -Boc保护基团的酸性水解。未优化的放化收率为5.7±1.35%，放化纯度大于99%，摩尔活度为100.7±34.5 GBq/μmol（ n =3）。 [ 18 F] 5在大鼠血浆中稳定至少4小时，并使用单侧喹啉酸大鼠神经炎症模型通过μPET成像和生物分布进行评估。时间-活性曲线显示[ 18 F] 5静脉注射后立即进入大脑，然后逐渐离开大脑，注射后30分钟达到很低的水平。生物分布研究显示，大脑受损侧和完整侧之间以及对照大鼠和用饱和剂量的 JNJ-7777120 作为特异性 H4R 拮抗剂预处理的动物之间，[ 18 F] 5的积累没有差异。因此，尽管 [ 18 F] 5在体外对 H4R 具有纳摩尔亲和力，并且能够穿过大鼠的血脑屏障，但它似乎不适合通过 PET 对受体进行体内成像。
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