title: A cell permeable peptide analog as a potential-specific PET imaging probe for prostate cancer detection.
abstract: Non-invasive detection of prostate cancer or metastases still remains a challenge in the field of molecular imaging. In our recent work of screening arginine- or lysine-rich peptides for intracellular delivery of a therapeutic agent into prostate cancer cells, an arginine-rich cell permeable peptide (NH(2)GR(11)) was found with an unexpectedly preferential uptake in prostate cancer cell lines. The goal of this work was to develop this peptide as a positron emission tomography (PET) imaging probe for specific detection of distant prostate cancer metastases. The optimal length of arginine-rich peptides was evaluated by the cell uptake efficiency of three fluorescein isothiocyanate (FITC)-tagged oligoarginines (NHGR(9), NHGR(11), and NHGR(13)) in four human prostate cell lines (LNCaP, PZ-HPV-7, DU145, and PC3). Of the three oligoarginines, NH(2)GR(11) showed the highest cell uptake and internalization efficiency with its subcellular localization in cytosol. The biodistribution of FITC-NHGR(9), FITC-NHGR(11), and FITC-NHGR(13) performed in control nude mice displayed the unique preferential accumulation of FITC-NHGR(11) in the prostate tissue. Further in vivo evaluation of FITC-NHGR(11) in PC3 tumor-bearing nude mice revealed elevated uptake of this peptide in tumors as compared to other organs. In vivo pharmacokinetics evaluated with (64)Cu-labeled NH(2)GR(11) showed that the peptide was rapidly cleared from the blood (t(1/2) = 10.7 min) and its elimination half-life was 17.2 h. The PET imaging specificity of (64)Cu-labled NH(2)GR(11) was demonstrated for the detection of prostate cancer in a comparative imaging experiment using two different human cancer xenograft models.
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Hao
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Long
authors.forename: Tiffani
authors.initials: T
authors.lastname: Anthony
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stanfield
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.forename: Xiankai
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000493:pharmacokinetics; D003301:Copper Radioisotopes / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015335:Molecular Probes / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000295:instrumentation* / Q000379:methods; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D057846:Cell-Penetrating Peptides; D003301:Copper Radioisotopes; D015335:Molecular Probes; D019275:Radiopharmaceuticals