αvβ3 Integrin-targeting radionuclide therapy and imaging with monomeric RGD peptide

✍ Scribed by Mitsuyoshi Yoshimoto; Kazuma Ogawa; Kohshin Washiyama; Naoto Shikano; Hirofumi Mori; Ryohei Amano; Keiichi Kawai

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 283 KB
• Volume: 123
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23575

✦ Synopsis

Abstract

The α~v~β~3~ integrin plays a pivotal role in angiogenesis and tumor metastasis. Angiogenic blood vessels overexpress α~v~β~3~ integrin, as in tumor neovascularization, and α~v~β~3~ integrin expression in other microvascular beds and organs is limited. Therefore, α~v~β~3~ integrin is a suitable receptor for tumor‐targeting imaging and therapy. Recently, tetrameric and dimeric RGD peptides have been developed to enhance specificity to α~v~β~3~ integrin. In comparison to the corresponding monomeric peptide, however, these peptides show high levels of accumulation in kidney and liver. The purpose of this study is to evaluate tumor‐targeting properties and the therapeutic potential of ^111^In‐ and ^90^Y‐labeled monomeric RGD peptides in BALB/c nude mice with SKOV‐3 human ovarian carcinoma tumors. DOTA‐c(RGDfK) was labeled with ^111^In or ^90^Y and purified by HPLC. A biodistribution study and scintigraphic images revealed the specific uptake to α~v~β~3~ integrin and the rapid clearance from normal tissues. These peptides were renally excreted. At 10 min after injection of tracers, ^111^In‐DOTA‐c(RGDfK) and ^90^Y‐DOTA‐c(RGDfK) showed high uptake in tumors (7.3 ± 0.6% ID/g and 4.6 ± 0.8% ID/g, respectively) and gradually decreased over time (2.3 ± 0.4% ID/g and 1.5 ± 0.5% ID/g at 24 hr, respectively). High tumor‐to‐blood and ‐muscle ratios were obtained from these peptides. In radionuclide therapeutic study, multiple‐dose administration of ^90^Y‐DOTA‐c(RGDfK) (3 × 11.1 MBq) suppressed tumor growth in comparison to the control group and a single‐dose administration (11.1 MBq). Monomeric RGD peptides, ^111^In‐DOTA‐c(RGDfK) and ^90^Y‐DOTA‐c(RGDfK), could be promising tracers for α~v~β~3~ integrin‐targeting imaging and radiotherapy. © 2008 Wiley‐Liss, Inc.