RGD-Human Serum Albumin Conjugates as Efficient Tumor Targeting Probes

被引:38
作者
Chen, Kai
Xie, Jin
Chen, Xiaoyuan [1 ]
机构
[1] Stanford Univ, Sch Med, Mol Imaging Program Stanford, Dept Radiol, Stanford, CA 94305 USA
来源
MOLECULAR IMAGING | 2009年 / 8卷 / 02期
关键词
INTEGRIN ALPHA(V)BETA(3); BOUND PACLITAXEL; QUANTUM DOTS; PEPTIDE; PET; EXPRESSION; VASCULATURE; ADENOVIRUS; TRANSPORT; MICROPET;
D O I
10.2310/7290.2009.00011
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Cyclic arginine-glycine-aspartate (RGD) peptides and their derivatives have been intensively studied as tumor targeting probes. One major drawback, however, is their short blood circulation half-lives, which greatly compromises their targeting efficacy. To address this issue, a cyclic peptide, c(RGDyK), and an organic dye (IRDyc800 or Cy5.5) were covalently conjugated onto human serum albumin (HSA). The conjugates were subjected to in vitro cell staining, in vivo near-infrared fluorescence (NIRF) imaging, ex vivo NIRF imaging, and histologic studies to evaluate their feasibility as tumor imaging probes. As a control, RAD peptide was also coupled with HSA and labeled with IRDye800 for in vivo imaging. The HSA-RGD-IRDye800 exhibited integrin alpha(v)beta(3)-specific binding in cell staining experiment. In vivo NIRF imaging showed higher tumor accumulation and tumor to background contrast of HSA-RGD-IRDye800 over RGD-IRDye800. The integrin specificity of HSA-RGD-IRDye800 is confirmed by both successful inhibition of tumor uptake in the presence of c(RGDyK) and the inability to accumulate in integrin-positive tumors by RAD-HSA-IRDye800. Histologic examination revealed initial tumor vascular binding and eventually both tumor vasculature and tumor cell integrin binding in vivo. In summary, we successfully developed an RGD-based protein conjugate with prolonged circulation half-life for NIRF imaging of tumor integrin alpha(v)beta(3) expression. The success of this study may be generalizable for other peptide-based probes to be conjugated with HSA for prolonged tumor contrast and improved pharmacokinetics.
引用
收藏
页码:65 / 73
页数:9
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