Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
Molecules. 2021 Oct 10;26(20):6107. doi: 10.3390/molecules26206107.
We recently developed I- and At-labeled monomer RGD peptides using a novel radiolabeling method. Both labeled peptides showed high accumulation in the tumor and exhibited similar biodistribution, demonstrating their usefulness for radiotheranostics. This study applied the labeling method to a dimer RGD peptide with the aim of gaining higher accumulation in tumor tissues based on improved affinity with αβ integrin. We synthesized an iodine-introduced dimer RGD peptide, E[c(RGDfK)] (), and an I-labeled dimer RGD peptide, E[c(RGDfK)]{[I]c[RGDf(4-I)K]} ([I]), and evaluated them as a preliminary step to the synthesis of an At-labeled dimer RGD peptide. The affinity of for αβ integrin was higher than that of a monomer RGD peptide. In the biodistribution experiment at 4 h postinjection, the accumulation of [I] (4.12 ± 0.42% ID/g) in the tumor was significantly increased compared with that of I-labeled monomer RGD peptide (2.93 ± 0.08% ID/g). Moreover, the accumulation of [I] in the tumor was greatly inhibited by co-injection of an excess RGD peptide. However, a single injection of [I] (11.1 MBq) did not inhibit tumor growth in tumor-bearing mice. We expect that the labeling method for targeted alpha therapy with At using a dimer RGD peptide could prove useful in future clinical applications.
我们最近开发了使用新型放射性标记方法标记的 I 和 At 标记的单体 RGD 肽。两种标记的肽在肿瘤中均表现出高积累，并表现出相似的生物分布，表明它们可用于放射治疗学。本研究应用该标记方法对二聚体 RGD 肽进行了研究，旨在基于与 αβ 整合素的亲和力提高，获得更高的肿瘤组织积累。我们合成了碘引入的二聚体 RGD 肽 Ec(RGDfK)和 I 标记的二聚体 RGD 肽 E[c(RGDfK)]{[I]c[RGDf(4-I)K]}([I])，并将其作为合成 At 标记的二聚体 RGD 肽的初步步骤进行了评估。与单体 RGD 肽相比，的 αβ 整合素亲和力更高。在注射后 4 小时的生物分布实验中，与 I 标记的单体 RGD 肽(2.93 ± 0.08% ID/g)相比，[I]在肿瘤中的积累明显增加(4.12 ± 0.42% ID/g)。此外，过量 RGD 肽共注射大大抑制了[I]在肿瘤中的积累。但是，单次注射[I](11.1 MBq)并不能抑制荷瘤小鼠的肿瘤生长。我们期望使用二聚体 RGD 肽进行靶向α治疗的 At 标记方法在未来的临床应用中证明是有用的。
