||Immunotargeting of Integrin α6β4 for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model.
U Winn, Aung ,
Tsuji, Atsushi ,
Sudo, Hitomi ,
Sugyo, Aya ,
Furukawa, Takako ,
Ukai, Yoshinori ,
Kurosawa, YoshikazuSaga, Tsuneo
To explore suitable imaging probes for early and specific detection of pancreatic cancer, we demonstrated that a6b4 integrin is agood target and employed single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging for immunotargeting.Expression levels of a6b4 were examined by Western blotting and flow cytometry in certain human pancreatic cancercell lines. The human cell line BxPC-3 was used for a6b4-positive and a mouse cell line, A4, was used for negative counterpart. Welabeled antibody against a6b4 with Indium-111 (111In) or indocyanine green (ICG). After injection of 111In-labeled probe to tumorbearingmice, biodistribution, SPECT, autoradiography (ARG), and immunohistochemical (IHC) studies were conducted. Afteradministration 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 probewashout in NIR imaging when compared to A4 tumor. The biodistribution profile of 111In-labeled probe, ARG, and IHC confirmedthe a6b4 specific binding of the probe. Here, we propose that a6b4 is a desirable target for the diagnosis of pancreatic cancer andthat it could be detected by radionuclide imaging and NIR imaging using a radiolabeled or ICG-labeled a6b4 antibody.