期刊
INFLAMMATORY BOWEL DISEASES
卷 16, 期 9, 页码 1458-1466出版社
OXFORD UNIV PRESS INC
DOI: 10.1002/ibd.21231
关键词
colitis; inflammatory bowel disease; radioimmunodetection; integrin targeting; copper-64
资金
- NIH [RC1 DK087348, AI063421, HL048675]
- The Leukemia and Lymphoma Society [6004]
- Alon Foundation
- European Union [IRG-FP7]
- National Cancer Institute [R24CA86307]
- CHMC Anesthesia Foundation
Background: The primary function of integrin beta(7) 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 beta(7) integrin with a radiolabeled antibody. Methods: FIB504.64, a monoclonal antibody that binds to beta(7) integrin, was conjugated with a bifunctional chelator and labeled with Cu-64. The antibody (50 mu g, 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 Cu-64-labeled nonspecific iso-type-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 Cu-64-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 Cu-64-labeled FIB504.64, 6.49 +/- 2.25; control mice with Cu-64-labeled FIB504.64, 3.64 +/- 1.12; colitis mice, Cu-64-labeled nonspecific antibody 3.97 +/- 0.48%ID/g (P < 0.05 between groups). Conclusions: The selective uptake of Cu-64-labeled FIB504.64 antibody in the gut of animals with colitis suggests that integrin beta(7) may be a promising target for radioimmunodetection of this disease, which would aid diagnosis, assessment, and therapy guidance of this disease.
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