title: Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) remains a major cause of cancer-related death. Since significant upregulation of αvβ6 integrin has been reported in PDAC, this integrin is a promising target for PDAC detection. In this study, we aimed to develop a radioiodinated probe for the imaging of αvβ6 integrin-positive PDAC with single-photon emission computed tomography (SPECT).
  
  
  METHODS
  Four peptide probes were synthesized and screened by competitive and saturation binding assays using 2 PDAC cell lines (AsPC-1, αvβ6 integrin-positive; MIA PaCa-2, αvβ6 integrin-negative). The probe showing the best affinity was used to study the biodistribution assay, an in vivo blocking study, and SPECT imaging using tumor bearing mice. Autoradiography and immunohistochemical analysis were also performed.
  
  
  RESULTS
  Among the 4 probes examined in this study, (125)I-IFMDV2 showed the highest affinity for αvβ6 integrin expressed in AsPC-1 cells and no affinity for MIA PaCa-2 cells. The accumulation of (125)I-IFMDV2 in the AsPC-1 xenograft was 3-5 times greater than that in the MIA PaCa-2 xenograft, consistent with the expression of αvβ6 integrin in each xenograft, and confirmed by immunohistochemistry. Pretreatment with excess amounts of A20FMDV2 significantly blocked the accumulation of (125)I-IFMDV2 in the AsPC-1 xenograft, but not in the MIA PaCa-2 xenograft. Furthermore, (123)I-IFMDV2 enabled clear visualization of the AsPC-1 xenograft.
  
  
  CONCLUSIONS
  (123)I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC.
authors.affiliation: Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan; Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; Radioisotope Research Center of Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Molecular Medicine Team, Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8568, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Molecular Medicine Team, Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8568, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ikehara
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. Electronic address: hsaji@pharm.kyoto-u.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D006801:Humans; D016023:Integrins / Q000032:analysis*; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008969:Molecular Sequence Data; D010179:Pancreas / Q000000981:diagnostic imaging / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm; D016023:Integrins; D007457:Iodine Radioisotopes; D010455:Peptides; C073878:integrin alphavbeta6
keywords: Nuclear medical imaging; Pancreatic ductal adenocarcinoma; Small animal SPECT/CT; αvβ6 Integrin