title: A radiolabeled nonapeptide probe targeting PC-3 cells and bone metastases of prostate cancer in mice.
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 (99m)Tc-DTPA-c(CGRRAGGSC) was radiolabeled with (99m)Tc 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, (99m) Tc-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 K(d) value was 0.32 ± 0.02 n m and the B(max) value was 754 ± 34 fmol mg(-1) pro. The probe exhibited a high tumor uptake in vivo. The radioactive molecular probe (99m) Tc-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.
authors.affiliation: Nuclear Medicine Technology Institute, School of Medicine, Southeast University, Road 87, Dingjiaqiao, Nanjing, 210009, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Qinghua
authors.forename: Xu
authors.initials: X
authors.lastname: Jianli
authors.forename: Liu
authors.initials: L
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zexuan
authors.forename: Tong
authors.initials: T
authors.lastname: Guansheng
authors.forename: Gao
authors.initials: G
authors.lastname: Hailin
authors.forename: Jiang
authors.initials: J
authors.lastname: Jianwei
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005453:Fluorescence; D006801:Humans; D008297:Male; D051379:Mice; D015335:Molecular Probes; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000473:pathology*; D011877:Radionuclide Imaging; D053702:Receptors, Interleukin-11 / Q000378:metabolism; D013669:Technetium Tc 99m Medronate; D016284:Technetium Tc 99m Pentetate; D014018:Tissue Distribution
chemical_list: D015335:Molecular Probes; D009842:Oligopeptides; D053702:Receptors, Interleukin-11; D016284:Technetium Tc 99m Pentetate; D013669:Technetium Tc 99m Medronate