Feni Lucia, Omrane M Aymen, Fischer Moritz, Zlatopolskiy Boris D, Neumaier Bernd, Neundorf Ines
Department of Chemistry, Biochemistry, Zülpicher Str. 47a, 50674 Cologne, Germany.
Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Jülich GmbH, Wilhelm-Johnen Str., 52425 Jülich, Germany.
Pharmaceuticals (Basel). 2017 Dec 18;10(4):99. doi: 10.3390/ph10040099.
Since pancreatic cancer is often diagnosed in a late state of cancer development, diagnostic opportunities allowing early disease detection are highly sought after. As such, cancer expression of claudin proteins is markedly dysregulated, making it an attractive target for molecular imaging like positron emission tomography (PET). Claudins are a family of transmembrane proteins that have a pivotal role as members of the tight junctions. In particular, claudin-3 and claudin-4 are frequently overexpressed in pancreatic cancer. F-Labeled claudin selective peptides would provide access to a novel kind of imaging tools for pancreatic cancer. In this work we describe the synthesis of the first F-labeled probes potentially suitable for PET imaging of claudin-4 expression. These probes were prepared using oxime ligation of 5-[F]fluoro-5-deoxyribose (5-[F]FDR) to claudin selective peptides. As a proof-of-principle, one of them, 5-[F]FDR-Clone 27, was isolated in >98% radiochemical purity and in 15% radiochemical yield (EOB) within 98 min, and with a molar activity of 4.0 GBq/μmol (for 30 MBq of tracer). Moreover, we present first biological data for the prepared 5-FDR-conjugates. These tracers could pave the way for an early diagnosis of pancreatic tumor, and thus improve the outcome of anticancer therapy.
由于胰腺癌往往在癌症发展的晚期才被诊断出来，因此能够实现早期疾病检测的诊断机会备受追捧。正因如此，claudin蛋白的癌症表达明显失调，使其成为正电子发射断层扫描（PET）等分子成像的一个有吸引力的靶点。Claudins是一类跨膜蛋白，作为紧密连接的成员发挥着关键作用。特别是，claudin-3和claudin-4在胰腺癌中经常过度表达。F标记的claudin选择性肽将为胰腺癌提供一种新型的成像工具。在这项工作中，我们描述了首个可能适用于PET成像claudin-4表达的F标记探针的合成。这些探针是通过将5-[F]氟-5-脱氧核糖（5-[F]FDR）与claudin选择性肽进行肟连接制备的。作为原理验证，其中一个探针5-[F]FDR-Clone 27在98分钟内以>98%的放射化学纯度和15%的放射化学产率（按校正后计算）被分离出来，摩尔活度为4.0 GBq/μmol（对于30 MBq的示踪剂）。此外，我们展示了所制备的5-FDR缀合物的首批生物学数据。这些示踪剂可为胰腺癌的早期诊断铺平道路，从而改善抗癌治疗的效果。
