Detection of intestinal inflammation by MicroPET imaging using a 64Cu-labeled anti-β7 integrin antibody

Jason L.J. Dearling, Eun Jeong Park, Patricia Dunning, Amanda Baker, Frederic Fahey, S. Ted Treves, Sulpicio G. Soriano, Motomu Shimaoka, Alan B. Packard, Dan Peer

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1458-1466
Number of pages9
JournalInflammatory bowel diseases
Volume16
Issue number9
DOIs
StatePublished - Sep 2010

Keywords

  • Colitis
  • Copper-64
  • Inflammatory bowel disease
  • Integrin targeting
  • Radio-immunodetection

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

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