Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma.

• 上田, 真史

• Fukushima, Takahiro

• Ogawa, Kei

• Kimura, Hiroyuki

• Ono, Masahiro

• Yamaguchi, Takashi

• Ikehara, Yuzuru

• 佐治, 英郎

抄録

[Introduction]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. [Conclusion][123]I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC.

収録刊行物

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 445 (3), 661-666, 2014-03-14

  Elsevier BV

キーワード

• αvβ6 Integrin
• Pancreatic ductal adenocarcinoma
• Small animal SPECT/CT
• Nuclear medical imaging
• Amino Acid Sequence
• Animals
• Antigens, Neoplasm/analysis
• Carcinoma, Pancreatic Ductal/diagnosis
• Carcinoma, Pancreatic Ductal/radionuclide imaging
• Cell Line, Tumor
• Humans
• Integrins/analysis
• Iodine Radioisotopes/chemistry
• Iodine Radioisotopes/diagnostic use
• Iodine Radioisotopes/pharmacokinetics
• Mice
• Molecular Sequence Data
• Pancreas/pathology
• Pancreas/radionuclide imaging
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/radionuclide imaging
• Peptides/chemical synthesis
• Peptides/chemistry
• Peptides/diagnostic use
• Peptides/pharmacokinetics
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon/methods

詳細情報

• CRID: 1050845760721644416
• NII論文ID: 120005466666
• NII書誌ID: AA00564395
• ISSN: 0006291X
• HANDLE: 2433/187093
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles