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

Masashi Ueda, Takahiro Fukushima, Kei Ogawa, Hiroyuki Kimura, Masahiro Ono, Takashi Yamaguchi, Yuzuru Ikehara, Hideo Saji

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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, 125I-IFMDV2 showed the highest affinity for αvβ6 integrin expressed in AsPC-1 cells and no affinity for MIA PaCa-2 cells. The accumulation of 125I-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 125I-IFMDV2 in the AsPC-1 xenograft, but not in the MIA PaCa-2 xenograft. Furthermore, 123I-IFMDV2 enabled clear visualization of the AsPC-1 xenograft. Conclusion: 123I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC.

Original languageEnglish
Pages (from-to)661-666
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume445
Issue number3
DOIs
Publication statusPublished - Mar 14 2014

Fingerprint

Integrins
Adenocarcinoma
Heterografts
Peptides
Single photon emission computed tomography
Single-Photon Emission-Computed Tomography
Imaging techniques
Assays
Bearings (structural)
Competitive Binding
Autoradiography
Tumors
Neoplasms
Up-Regulation
Visualization
Immunohistochemistry
Cells
Cell Line

Keywords

  • Nuclear medical imaging
  • Pancreatic ductal adenocarcinoma
  • Small animal SPECT/CT
  • αvβ6 Integrin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma. / Ueda, Masashi; Fukushima, Takahiro; Ogawa, Kei; Kimura, Hiroyuki; Ono, Masahiro; Yamaguchi, Takashi; Ikehara, Yuzuru; Saji, Hideo.

In: Biochemical and Biophysical Research Communications, Vol. 445, No. 3, 14.03.2014, p. 661-666.

Research output: Contribution to journalArticle

Ueda, Masashi ; Fukushima, Takahiro ; Ogawa, Kei ; Kimura, Hiroyuki ; Ono, Masahiro ; Yamaguchi, Takashi ; Ikehara, Yuzuru ; Saji, Hideo. / Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 445, No. 3. pp. 661-666.
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abstract = "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, 125I-IFMDV2 showed the highest affinity for αvβ6 integrin expressed in AsPC-1 cells and no affinity for MIA PaCa-2 cells. The accumulation of 125I-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 125I-IFMDV2 in the AsPC-1 xenograft, but not in the MIA PaCa-2 xenograft. Furthermore, 123I-IFMDV2 enabled clear visualization of the AsPC-1 xenograft. Conclusion: 123I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC.",
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T1 - Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma

AU - Ueda, Masashi

AU - Fukushima, Takahiro

AU - Ogawa, Kei

AU - Kimura, Hiroyuki

AU - Ono, Masahiro

AU - Yamaguchi, Takashi

AU - Ikehara, Yuzuru

AU - Saji, Hideo

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N2 - 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, 125I-IFMDV2 showed the highest affinity for αvβ6 integrin expressed in AsPC-1 cells and no affinity for MIA PaCa-2 cells. The accumulation of 125I-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 125I-IFMDV2 in the AsPC-1 xenograft, but not in the MIA PaCa-2 xenograft. Furthermore, 123I-IFMDV2 enabled clear visualization of the AsPC-1 xenograft. Conclusion: 123I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC.

AB - 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, 125I-IFMDV2 showed the highest affinity for αvβ6 integrin expressed in AsPC-1 cells and no affinity for MIA PaCa-2 cells. The accumulation of 125I-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 125I-IFMDV2 in the AsPC-1 xenograft, but not in the MIA PaCa-2 xenograft. Furthermore, 123I-IFMDV2 enabled clear visualization of the AsPC-1 xenograft. Conclusion: 123I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC.

KW - Nuclear medical imaging

KW - Pancreatic ductal adenocarcinoma

KW - Small animal SPECT/CT

KW - αvβ6 Integrin

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