Immunotargeting of Integrin αβ for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model

To explore suitable imaging probes for early and specific detection of pancreatic cancer, we demonstrated that α 6 β 4 integrin is a good target and employed single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging for immunotargeting. Expression levels of α 6 β 4 were exami...

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Main Authors: Winn Aung MBBS, PhD, Atsushi B. Tsuji PhD, Hitomi Sudo PhD, Aya Sugyo M.Ed, Takako Furukawa PhD, Yoshinori Ukai PhD, Yoshikazu Kurosawa PhD, Tsuneo Saga MD, PhD
Format: Article
Language:English
Published: SAGE Publishing 2016-01-01
Series:Molecular Imaging
Online Access:https://doi.org/10.1177/1536012115624917
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author Winn Aung MBBS, PhD
Atsushi B. Tsuji PhD
Hitomi Sudo PhD
Aya Sugyo M.Ed
Takako Furukawa PhD
Yoshinori Ukai PhD
Yoshikazu Kurosawa PhD
Tsuneo Saga MD, PhD
author_facet Winn Aung MBBS, PhD
Atsushi B. Tsuji PhD
Hitomi Sudo PhD
Aya Sugyo M.Ed
Takako Furukawa PhD
Yoshinori Ukai PhD
Yoshikazu Kurosawa PhD
Tsuneo Saga MD, PhD
author_sort Winn Aung MBBS, PhD
collection DOAJ
description To explore suitable imaging probes for early and specific detection of pancreatic cancer, we demonstrated that α 6 β 4 integrin is a good target and employed single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging for immunotargeting. Expression levels of α 6 β 4 were examined by Western blotting and flow cytometry in certain human pancreatic cancer cell lines. The human cell line BxPC-3 was used for α 6 β 4 -positive and a mouse cell line, A4, was used for negative counterpart. We labeled antibody against α 6 β 4 with Indium-111 ( 111 In) or indocyanine green (ICG). After injection of 111 In-labeled probe to tumor-bearing mice, biodistribution, SPECT, autoradiography (ARG), and immunohistochemical (IHC) studies were conducted. After administration of ICG-labeled probe, in vivo and ex vivo NIR imaging and fluorescence microscopy of tumors were performed. BxPC-3 tumor showed a higher radioligand binding in SPECT and higher fluorescence intensity as well as a delay in the probe washout in NIR imaging when compared to A4 tumor. The biodistribution profile of 111 In-labeled probe, ARG, and IHC confirmed the α 6 β 4 specific binding of the probe. Here, we propose that α 6 β 4 is a desirable target for the diagnosis of pancreatic cancer and that it could be detected by radionuclide imaging and NIR imaging using a radiolabeled or ICG-labeled α 6 β 4 antibody.
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spelling doaj-art-3f222c3e446e4dc4a57ee9b0d3c069722025-01-03T00:11:32ZengSAGE PublishingMolecular Imaging1536-01212016-01-011510.1177/153601211562491710.1177_1536012115624917Immunotargeting of Integrin αβ for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer ModelWinn Aung MBBS, PhD0Atsushi B. Tsuji PhD1Hitomi Sudo PhD2Aya Sugyo M.Ed3Takako Furukawa PhD4Yoshinori Ukai PhD5Yoshikazu Kurosawa PhD6Tsuneo Saga MD, PhD7Diagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, JapanDiagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, JapanDiagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, JapanDiagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, JapanDiagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, JapanPerseus Proteomics Inc, Tokyo, JapanInnovation Center for Advanced Medicine, Fujita Health University, Toyoake, JapanDiagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, JapanTo explore suitable imaging probes for early and specific detection of pancreatic cancer, we demonstrated that α 6 β 4 integrin is a good target and employed single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging for immunotargeting. Expression levels of α 6 β 4 were examined by Western blotting and flow cytometry in certain human pancreatic cancer cell lines. The human cell line BxPC-3 was used for α 6 β 4 -positive and a mouse cell line, A4, was used for negative counterpart. We labeled antibody against α 6 β 4 with Indium-111 ( 111 In) or indocyanine green (ICG). After injection of 111 In-labeled probe to tumor-bearing mice, biodistribution, SPECT, autoradiography (ARG), and immunohistochemical (IHC) studies were conducted. After administration of ICG-labeled probe, in vivo and ex vivo NIR imaging and fluorescence microscopy of tumors were performed. BxPC-3 tumor showed a higher radioligand binding in SPECT and higher fluorescence intensity as well as a delay in the probe washout in NIR imaging when compared to A4 tumor. The biodistribution profile of 111 In-labeled probe, ARG, and IHC confirmed the α 6 β 4 specific binding of the probe. Here, we propose that α 6 β 4 is a desirable target for the diagnosis of pancreatic cancer and that it could be detected by radionuclide imaging and NIR imaging using a radiolabeled or ICG-labeled α 6 β 4 antibody.https://doi.org/10.1177/1536012115624917
spellingShingle Winn Aung MBBS, PhD
Atsushi B. Tsuji PhD
Hitomi Sudo PhD
Aya Sugyo M.Ed
Takako Furukawa PhD
Yoshinori Ukai PhD
Yoshikazu Kurosawa PhD
Tsuneo Saga MD, PhD
Immunotargeting of Integrin αβ for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model
Molecular Imaging
title Immunotargeting of Integrin αβ for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model
title_full Immunotargeting of Integrin αβ for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model
title_fullStr Immunotargeting of Integrin αβ for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model
title_full_unstemmed Immunotargeting of Integrin αβ for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model
title_short Immunotargeting of Integrin αβ for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model
title_sort immunotargeting of integrin αβ for single photon emission computed tomography and near infrared fluorescence imaging in a pancreatic cancer model
url https://doi.org/10.1177/1536012115624917
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