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

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.