Department of Nuclear Medicine, University Hospital of Würzburg, Oberdürrbacher Strasse 6, 97080, Würzburg, Germany.
Comprehensive Heart Failure Center, University Hospital of Würzburg, Würzburg, Germany.
Mol Imaging Biol. 2020 Jun;22(3):602-611. doi: 10.1007/s11307-019-01407-5.
Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential applications in the diagnosis and assessment of cardiac sympathetic nerve conditions as well as the delineation of neuroendocrine tumours. However, to date, none have been used clinically. Drawbacks of currently reported radiotracers include suboptimal kinetics and challenging radiolabelling procedures.
We developed a novel fluorine-18-labelled radiotracer targeting NET, AF78, with efficient one-step radiolabelling based on the phenethylguanidine structure. Radiosynthesis of AF78 was undertaken, followed by validation in cell uptake studies, autoradiography, and in vivo imaging in rats.
[F]AF78 was successfully synthesized with 27.9 ± 3.1 % radiochemical yield, > 97 % radiochemical purity and > 53.8 GBq/mmol molar activity. Cell uptake studies demonstrated essentially identical affinity for NET as norepinephrine and meta-iodobenzylgaunidine. Both ex vivo autoradiography and in vivo imaging in rats showed homogeneous and specific cardiac uptake.
The new PET radiotracer [F]AF78 demonstrated high affinity for NET and favourable biodistribution in rats. A structure-activity relationship between radiotracer structures and affinity for NET was revealed, which may serve as the basis for the further design of NET targeting radiotracers with favourable features.
充分利用正电子发射断层扫描（PET）技术，氟-18 标记的去甲肾上腺素转运体（NET）放射性示踪剂在心脏交感神经状况的诊断和评估以及神经内分泌肿瘤的描绘方面具有潜在的应用。然而，迄今为止，尚未在临床上使用。目前报道的放射性示踪剂的缺点包括动力学不理想和放射性标记程序具有挑战性。
我们开发了一种新型的氟-18 标记的 NET 靶向放射性示踪剂 AF78，基于苯乙胍结构，采用高效的一步放射性标记。进行了 AF78 的放射合成，随后进行了细胞摄取研究、放射自显影以及大鼠体内成像的验证。
[F]AF78 的合成产率为 27.9±3.1%，放射化学纯度>97%，摩尔比活度>53.8GBq/mmol。细胞摄取研究表明，其对 NET 的亲和力与去甲肾上腺素和间碘苄胍基本相同。离体放射自显影和大鼠体内成像均显示出均匀且特异性的心脏摄取。
新型 PET 放射性示踪剂[F]AF78 对 NET 具有高亲和力，并在大鼠体内具有良好的分布。揭示了放射性示踪剂结构与 NET 亲和力之间的构效关系，这可能为进一步设计具有良好特性的 NET 靶向放射性示踪剂提供基础。
