open access

https://hdl.handle.net/2115/97548

Design of a tetravalent RGD peptide capable of simultaneous binding with multiple integrin αvβ3 for targeted radionuclide therapy

英語

Astatine-211

2025-03-13

American Chemical Society

Journal of medicinal chemistry

68(6)

6518-6533

For targeted radionuclide therapy, radioligands that exhibit high and persistent tumor uptake are indispensable. We previously synthesized a Tc-99m-labeled hexavalent RGD peptide (Tc-99m-(RGD)(6)) as a tumor imaging agent targeting integrin alpha v beta 3. Tc-99m-(RGD)(6) showed high in vivo tumor uptake with long retention due to simultaneous binding to multiple integrin alpha v beta 3 receptors. The purpose of this study was to apply this finding to the design of a multivalent RGD peptide labeled with At-211, a promising alpha-emitting radionuclide for radionuclide therapy. As a candidate compound, a tetravalent RGD peptide (H2N-(RGD)(4)) was synthesized and radiolabeled with I-125, a homologous element of At, for basic studies. As expected, I-125-(RGD)(4) retained the capability of simultaneous binding and showed comparable in vivo tumor uptake to Tc-99m-(RGD)(6). Finally, At-211-(RGD)(4) was synthesized with >95% radiochemical purity and exhibited an almost identical biodistribution pattern to I-125-(RGD)(4). These results indicate that At-211-(RGD)(4) might be a potential radioligand for integrin alpha v beta 3-targeted radionuclide therapy.

学術雑誌論文

Accepted Manuscript

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/articlesonrequest/AOR-SYA6NYIMRSKHVHHMWSPD.

0022-2623