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A radiolabeled nonapeptide probe targeting PC-3 cells and bone metastases of prostate cancer in mice

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Abstract

Previous investigations showed that interleukin-11 (IL-11) and the IL-11 receptor (IL-11R) are correlated with regulation of tumor progression and may play significant roles in bone metastases. The nonapeptide structure c(CGRRAGGSC) is a phage-display-selected IL-11 mimic that binds to IL-11R. The aim of this study was to synthesize radiolabeled c(CGRRAGGSC) and to investigate the possible interaction between this radioactive probe and an IL-11R-positive bone metastasis model of PC-3 prostate cancer. The molecular probe 99mTc–DTPA–c(CGRRAGGSC) was radiolabeled with 99mTc using the diethylenetriaminepentaacetic acid (DTPA) chelate. Counterstaining was performed with LSS670, a near-infrared dye. The binding sites of the molecular probe in PC-3 cells were observed under a fluorescence microscope. The binding characteristics of the labeled probe were analyzed using radioreceptor analysis. Single photon emission tomography imaging and biodistribution of the probe were investigated using xenografts of PC-3 cells into tibias of nude mice. The labeled product, 99mTc–DTPA–c(CGRRAGGSC), was obtained with high labeling efficiency, high radiochemical purity and good stability. The molecular probe was combined with the PC-3 cell membrane and cytoplasm through fluorescence tracing. In the saturation and competitive inhibition experiments performed in vitro, the Kd value was 0.32 ± 0.02 n m and the Bmax value was 754 ± 34 fmol mg−1 pro. The probe exhibited a high tumor uptake in vivo. The radioactive molecular probe 99mTc–DTPA–c(CGRRAGGSC) may be used as a specific molecular imaging agent for detecting IL-11R overexpression in tumors and bone metastasis, such as prostate cancers. Copyright © 2012 John Wiley & Sons, Ltd.

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