Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Chembiochem. 2021 Apr 6;22(7):1307-1315. doi: 10.1002/cbic.202000791. Epub 2021 Jan 4.
Multimodal imaging probes have attracted the interest of ongoing research, for example, for the surgical removal of tumors. Modular synthesis approaches allow the construction of hybrid probes consisting of a radiotracer, a fluorophore and a targeting unit. We present the synthesis of a new asymmetric bifunctional cyanine dye that can be used as a structural and functional linker for the construction of such hybrid probes. Ga-DOTATATE, a well-characterized radiopeptide targeting the overexpressed somatostatin receptor subtype 2 (SSTR2) in neuroendocrine tumors, was labeled with our cyanine dye, thus providing additional information along with the data obtained from the radiotracer. We tested the SSTR2-targeting and imaging properties of the resulting probe Ga-DOTA-ICC-TATE in vitro and in a tumor xenograft mouse model. Despite the close proximity between dye and pharmacophore, we observed a high binding affinity towards SSTR2 as well as elevated uptake in SSTR2-overexpressing tumors in the positron emission tomography (PET) scan and histological examination.
多模态成像探针引起了正在进行的研究的兴趣，例如用于肿瘤的手术切除。模块化合成方法允许构建由放射性示踪剂、荧光团和靶向单元组成的混合探针。我们提出了一种新的不对称双功能菁染料的合成方法，该染料可用作构建此类混合探针的结构和功能连接体。Ga-DOTATATE 是一种经过充分表征的放射性肽，靶向神经内分泌肿瘤中过度表达的生长抑素受体亚型 2 (SSTR2)，用我们的菁染料进行标记，从而提供了放射性示踪剂获得的数据之外的其他信息。我们在体外和肿瘤异种移植小鼠模型中测试了所得探针 Ga-DOTA-ICC-TATE 的 SSTR2 靶向和成像特性。尽管染料和药效团之间非常接近，但我们观察到对 SSTR2 的高结合亲和力以及在 SSTR2 过表达肿瘤中的摄取增加，这在正电子发射断层扫描 (PET) 扫描和组织学检查中得到了证实。
