title: Characterization of TCP-1 probes for molecular imaging of colon cancer.
abstract: Molecular probes capable of detecting colorectal cancer (CRC) are needed for early CRC diagnosis. The objective of this study was to characterize c[CTPSPFSHC]OH (TCP-1), a small peptide derived from phage display selection, for targeting human CRC xenografts using technetium-99m ((99m)Tc)-labeled TCP-1 and fluorescent cyanine-7 (Cy7)-labeled form of the peptide (Cy7-TCP-1). (99m)Tc-TCP-1 was generated by modifying TCP-1 with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC) followed by radiolabeling. In vitro saturation binding experiments were performed for (99m)Tc-TCP-1 in human HCT116 colon cancer cells. SCID mice with human HCT116 cancer xenografts were imaged with (99m)Tc-TCP-1 or control peptide using a small-animal SPECT imager: Group I (n=5) received no blockade; Group II (n=5) received a blocking dose of non-radiolabeled TCP-1. Group III (n=5) were imaged with (99m)Tc-labeled control peptide (inactive peptide). SCID mice with human PC3 prostate cancer xenografts (Group IV, n=5) were also imaged with (99m)Tc-TCP-1. Eight additional SCID mice bearing HCT116 xenografts in dorsal skinfold window chambers (DSWC) were imaged by direct positron imaging of (18)F-fluorodeoxyglucose ((18)F-FDG) and fluorescence microscopy of Cy7-TCP-1. In vitro(99m)Tc-HYNIC-TCP-1 binding assays on HCT 116 cells indicated a mean Kd of 3.04±0.52nM. In cancer xenografts, (99m)Tc-TCP-1 radioactivity (%ID/g) was 1.01±0.15 in the absence of blockade and was reduced to 0.26±0.04 (P<0.01) with blockade. No radioactive uptake was observed in the PC3 tumors with (99m)Tc-TCP-1 or HCT116 tumors with inactive peptide. Cy7-TCP-1 activity localized not only in metabolically active tumors, as defined by (18)F-FDG imaging, but also in peritumoral microvasculature. In conclusion, TCP-1 probes may have a distinct targeting mechanism with high selectivity for CRC and tumor-associated vasculature. Molecular imaging with TCP-1 probes appears promising to detect malignant colorectal lesions.
authors: Department of Medical Imaging, The University of Arizona, Tucson, AZ, United States. Electronic address: zliu@email.arizona.edu.
authors: Zhonglin
authors: Z
authors: Liu
authors: Molecular Targeting Technologies, Inc., West Chester, PA, United States.
authors: Brian D
authors: BD
authors: Gray
authors: Department of Medical Imaging, The University of Arizona, Tucson, AZ, United States.
authors: Christy
authors: C
authors: Barber
authors: Department of Surgery, The University of Arizona, Tucson, AZ, United States.
authors: Michael
authors: M
authors: Bernas
authors: Department of Chemistry & Biochemistry, The University of Arizona, Tucson, AZ, United States.
authors: Minying
authors: M
authors: Cai
authors: Department of Medical Imaging, The University of Arizona, Tucson, AZ, United States; College of Optical Sciences, The University of Arizona, Tucson, AZ, United States.
authors: Lars R
authors: LR
authors: Furenlid
authors: Department of Medical Imaging, The University of Arizona, Tucson, AZ, United States.
authors: Andrew
authors: A
authors: Rouse
authors: Department of Pathology, The University of Arizona, Tucson, AZ, United States.
authors: Charmi
authors: C
authors: Patel
authors: Department of Medicine, The University of Arizona, Tucson, AZ, United States; Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, United States; College of Optical Sciences, The University of Arizona, Tucson, AZ, United States.
authors: Bhaskar
authors: B
authors: Banerjee
authors: College of Optical Sciences, The University of Arizona, Tucson, AZ, United States.
authors: Rongguang
authors: R
authors: Liang
authors: Department of Medical Imaging, The University of Arizona, Tucson, AZ, United States; Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, United States; College of Optical Sciences, The University of Arizona, Tucson, AZ, United States.
authors: Arthur F
authors: AF
authors: Gmitro
authors: Department of Surgery, The University of Arizona, Tucson, AZ, United States.
authors: Marlys H
authors: MH
authors: Witte
authors: Molecular Targeting Technologies, Inc., West Chester, PA, United States.
authors: Koon Y
authors: KY
authors: Pak
authors: Department of Medical Imaging, The University of Arizona, Tucson, AZ, United States.
authors: James M
authors: JM
authors: Woolfenden
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D057054:Molecular Imaging / Q000379:methods*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D013667:Technetium / Q000008:administration & dosage* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D010446:Peptide Fragments; D013667:Technetium
keywords: (99m)Tc; Colorectal cancer; Molecular imaging; Mouse xenograft models; Peptide; SPECT