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α v β 3 Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide
Author(s) -
Yoshimoto Mitsuyoshi,
Ogawa Kazuma,
Washiyama Kohshin,
Shikano Naoto,
Mori Hirofumi,
Amano Ryohei,
Kawai Keiichi
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23575
Subject(s) - dota , biodistribution , integrin , peptide , alpha (finance) , radionuclide therapy , cancer research , angiogenesis , chemistry , spect imaging , neovascularization , metastasis , medicine , receptor , nuclear medicine , cancer , biochemistry , in vitro , chelation , organic chemistry , construct validity , nursing , patient satisfaction
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.