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Title: Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma.
Authors: Ueda, Masashi
Fukushima, Takahiro
Ogawa, Kei
Kimura, Hiroyuki
Ono, Masahiro  kyouindb  KAKEN_id
Yamaguchi, Takashi
Ikehara, Yuzuru
Saji, Hideo  kyouindb  KAKEN_id
Author's alias: 上田, 真史
佐治, 英郎
Keywords: αvβ6 Integrin
Pancreatic ductal adenocarcinoma
Small animal SPECT/CT
Nuclear medical imaging
Issue Date: 14-Mar-2014
Publisher: Elsevier Inc.
Journal title: Biochemical and biophysical research communications
Volume: 445
Issue: 3
Start page: 661
End page: 666
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, [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.
Rights: © 2014 Elsevier Inc.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
DOI(Published Version): 10.1016/j.bbrc.2014.02.086
PubMed ID: 24583127
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