Development and evaluation of a theranostic probe with RGD peptide introduced platinum complex to enable tumor-specific accumulation

Hiroaki Echigo; Kenji Mishiro; Masayuki Munekane; Takeshi Fuchigami; Yoji Kitamura; Seigo Kinuya; Kazuma Ogawa

doi:10.1016/j.bmc.2022.116919

Development and evaluation of a theranostic probe with RGD peptide introduced platinum complex to enable tumor-specific accumulation

Bioorg Med Chem. 2022 Sep 15:70:116919. doi: 10.1016/j.bmc.2022.116919. Epub 2022 Jul 5.

Authors

Hiroaki Echigo¹, Kenji Mishiro², Masayuki Munekane¹, Takeshi Fuchigami¹, Yoji Kitamura³, Seigo Kinuya⁴, Kazuma Ogawa⁵

Affiliations

¹ Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
² Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
³ Research Center for Experimental Modeling of Human Disease, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa 920-8640, Japan.
⁴ Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa 920-8641, Japan.
⁵ Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan; Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan. Electronic address: kogawa@p.kanazawa-u.ac.jp.

PMID: 35816895
DOI: 10.1016/j.bmc.2022.116919

Abstract

Cisplatin (CDDP) has been widely used for chemotherapy. However, it has several unfavorable side effects due to its low tumor selectivity. In this study, we designed, synthesized, and evaluated Pt(IV)-[c(RGDyK)]₂ (9), in which two molecules of an RGD peptide are introduced as a carrier molecule to cancer into oxoplatin, a Pt(IV) prodrug of CDDP, to enhance cancer selectivity. Furthermore, we prepared and evaluated Pt(IV)-[c(RGDyK)]{[¹²⁵I]c[RGDy(3-I)K]} ([¹²⁵I]10) for a preliminary step of nuclear medicine imaging and theranostics. Compound 9 inhibited cell growth in the cell viability assay and, [¹²⁵I]10 was highly accumulated in tumor tissues (1 h: 3.53 ± 0.53 %ID/g) in the biodistribution study. These results indicate that implementing RGD peptides into oxoplatin enabled tumor-specific accumulation, and combining [^123/124I]10 and 9 for diagnostic imaging and therapy could be useful for cancer theranostics.

Keywords: Integrin; Platinum complex; RGD peptide; Theranostics; Tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Humans
Neoplasms* / drug therapy
Oligopeptides / chemistry
Platinum* / chemistry
Precision Medicine
Tissue Distribution

Substances

Oligopeptides
Platinum
arginyl-glycyl-aspartic acid