King's College London, Institute of Pharmaceutical Science, Franklin Wilkins Building, London SE1 9NH, UK.
Department of Drug and Health Sciences, University of Catania, Catania, Italy.
Dalton Trans. 2022 Aug 30;51(34):12796-12803. doi: 10.1039/d2dt00980c.
Expression of the cellular transmembrane receptor αvβ6 integrin is mostly restricted to malignant epithelial cells in a wide variety of carcinomas, including pancreatic and others derived from epithelial tissues. Thus, this protein is considered an attractive target for tumour imaging and therapy. Two different Ga hexadentate tris (3,4-hydroxypyridinone) (THP) chelators were produced in this study and coupled to the αvβ6 integrin-selective peptide (FRGDLAFp(NMe)K) NHS chemistry. Radiolabelling experiments confirmed a high radiochemical yield of the two PET probes. In addition, cellular binding studies showed high binding affinities in the nanomolar range. The two integrin αvβ6-peptide-THP synthesized and radiolabeled in this study will facilitate monitoring of transmembrane receptor αvβ6 integrin by using the advantage of THP chemistry for rapid, efficient and stable gallium chelation.
细胞跨膜受体 αvβ6 整联蛋白的表达大多局限于多种癌中的恶性上皮细胞，包括胰腺和其他源自上皮组织的癌。因此，该蛋白被认为是肿瘤成像和治疗的有吸引力的靶标。本研究中制备了两种不同的 Ga 六齿合三（3,4-羟基吡啶酮）（THP）螯合剂，并通过 NHS 化学与 αvβ6 整联蛋白选择性肽（FRGDLAFp（NMe）K）偶联。放射性标记实验证实了两种 PET 探针具有很高的放射化学产率。此外，细胞结合研究表明，它们具有纳摩尔范围内的高结合亲和力。本研究中合成和放射性标记的两种整合素 αvβ6-肽-THP 将通过利用 THP 化学的优势，实现对跨膜受体 αvβ6 整联蛋白的快速、高效和稳定的镓螯合作用，从而便于监测。
