TY - JOUR
T1 - Detection of intestinal inflammation by MicroPET imaging using a 64Cu-labeled anti-β7 integrin antibody
AU - Dearling, Jason L.J.
AU - Park, Eun Jeong
AU - Dunning, Patricia
AU - Baker, Amanda
AU - Fahey, Frederic
AU - Treves, S. Ted
AU - Soriano, Sulpicio G.
AU - Shimaoka, Motomu
AU - Packard, Alan B.
AU - Peer, Dan
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2010/9
Y1 - 2010/9
N2 - Background: The primary function of integrin β7 is the recruitment and retention of lymphocytes to the inflamed gut. The aim of this study was to investigate the possibility of imaging colitis radioimmunodetection by targeting the β7 integrin with a radiolabeled antibody. Methods: FIB504.64, a monoclonal antibody that binds to β7 integrin, was conjugated with a bifunctional chelator and labeled with 64Cu. The antibody (50 μg, 7 MBq) was injected into C57BL/6 mice with experimentally induced colitis (n = 6). MicroPET images were collected at 1, 24, and 48 hours postinjection and the biodistribution was measured at 48 hours by tissue assay. Data were also obtained for a 64Cu-labeled nonspecific isotype-matched antibody in mice with colitis and 64Cu-labeled FIB504.64 in healthy mice (n = 5-6). Results: The microPET images showed higher uptake of 64Cu-labeled FIB504.64 in the gut of mice with colitis than for either of the controls. This observation was confirmed by the 48-hour ex vivo biodistribution data: the percentage of injected dose per gram of tissue (%ID/g ± SD) (large intestine) colitis mice with 64Cu-labeled FIB504.64, 6.49 ± 2.25; control mice with 64Cu-labeled FIB504.64, 3.64 ± 1.12; colitis mice, 64Cu-labeled nonspecific antibody 3.97 ± 0.48%ID/g (P < 0.05 between groups). Conclusions: The selective uptake of 64Cu- labeled FIB504.64 antibody in the gut of animals with colitis suggests that integrin β7 may be a promising target for radioimmunodetection of this disease, which would aid diagnosis, assessment, and therapy guidance of this disease.
AB - Background: The primary function of integrin β7 is the recruitment and retention of lymphocytes to the inflamed gut. The aim of this study was to investigate the possibility of imaging colitis radioimmunodetection by targeting the β7 integrin with a radiolabeled antibody. Methods: FIB504.64, a monoclonal antibody that binds to β7 integrin, was conjugated with a bifunctional chelator and labeled with 64Cu. The antibody (50 μg, 7 MBq) was injected into C57BL/6 mice with experimentally induced colitis (n = 6). MicroPET images were collected at 1, 24, and 48 hours postinjection and the biodistribution was measured at 48 hours by tissue assay. Data were also obtained for a 64Cu-labeled nonspecific isotype-matched antibody in mice with colitis and 64Cu-labeled FIB504.64 in healthy mice (n = 5-6). Results: The microPET images showed higher uptake of 64Cu-labeled FIB504.64 in the gut of mice with colitis than for either of the controls. This observation was confirmed by the 48-hour ex vivo biodistribution data: the percentage of injected dose per gram of tissue (%ID/g ± SD) (large intestine) colitis mice with 64Cu-labeled FIB504.64, 6.49 ± 2.25; control mice with 64Cu-labeled FIB504.64, 3.64 ± 1.12; colitis mice, 64Cu-labeled nonspecific antibody 3.97 ± 0.48%ID/g (P < 0.05 between groups). Conclusions: The selective uptake of 64Cu- labeled FIB504.64 antibody in the gut of animals with colitis suggests that integrin β7 may be a promising target for radioimmunodetection of this disease, which would aid diagnosis, assessment, and therapy guidance of this disease.
KW - Colitis
KW - Copper-64
KW - Inflammatory bowel disease
KW - Integrin targeting
KW - Radio-immunodetection
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U2 - 10.1002/ibd.21231
DO - 10.1002/ibd.21231
M3 - Article
C2 - 20186943
AN - SCOPUS:77952379044
VL - 16
SP - 1458
EP - 1466
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
SN - 1078-0998
IS - 9
ER -