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

Abstract

AbstractThe αvβ3 integrin plays a pivotal role in angiogenesis and tumor metastasis. Angiogenic blood vessels overexpress αvβ3 integrin, as in tumor neovascularization, and αvβ3 integrin expression in other microvascular beds and organs is limited. Therefore, αvβ3 integrin is a suitable receptor for tumor‐targeting imaging and therapy. Recently, tetrameric and dimeric RGD peptides have been developed to enhance specificity to αvβ3 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 111In‐ and 90Y‐labeled monomeric RGD peptides in BALB/c nude mice with SKOV‐3 human ovarian carcinoma tumors. DOTA‐c(RGDfK) was labeled with 111In or 90Y and purified by HPLC. A biodistribution study and scintigraphic images revealed the specific uptake to αvβ3 integrin and the rapid clearance from normal tissues. These peptides were renally excreted. At 10 min after injection of tracers, 111In‐DOTA‐c(RGDfK) and 90Y‐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 90Y‐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, 111In‐DOTA‐c(RGDfK) and 90Y‐DOTA‐c(RGDfK), could be promising tracers for αvβ3 integrin‐targeting imaging and radiotherapy. © 2008 Wiley‐Liss, Inc.