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Detection of intestinal inflammation by MicroPET imaging using a (64)Cu-labeled anti-beta(7) integrin antibody
Jason L J Dearling1, Eun Jeong Park, Patricia Dunning
1Division of Nuclear Medicine, Department of Radiology, Children's Hospital, Boston, Massachusetts 02115, USA. jason.dearling@childrens.harvard.edu
Insights
Radioimmunodetection targeting beta(7) integrin shows promise for diagnosing colitis. A radiolabeled antibody, (64)Cu-FIB504.64, demonstrated selective uptake in the inflamed gut of mice, aiding disease assessment.
Area of Science:
- Medical Imaging
- Immunology
- Gastroenterology
Background:
- Integrin beta(7) plays a key role in lymphocyte homing to the inflamed gut.
- Targeting beta(7) integrin offers a potential strategy for imaging inflammatory bowel diseases.
Purpose of the Study:
- To evaluate the feasibility of radioimmunodetection of colitis using a radiolabeled antibody against beta(7) integrin.
Main Methods:
- A monoclonal antibody (FIB504.64) targeting beta(7) integrin was labeled with Copper-64 ((64)Cu).
- MicroPET imaging and biodistribution studies were performed in mice with experimentally induced colitis and control groups.
Main Results:
- MicroPET imaging revealed significantly higher uptake of (64)Cu-labeled FIB504.64 in the gut of colitis mice compared to controls.
- Ex vivo biodistribution confirmed selective accumulation of the radiolabeled antibody in the large intestine of mice with colitis.
Conclusions:
- Selective uptake of (64)Cu-labeled FIB504.64 in the inflamed gut suggests beta(7) integrin is a viable target for colitis radioimmunodetection.
- This approach could enhance diagnosis, assessment, and therapy guidance for colitis.
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 (64)Cu. The antibody (50 microg, 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 (64)Cu-labeled nonspecific isotype-matched antibody in mice with colitis and (64)Cu-labeled FIB504.64 in healthy mice (n = 5-6).
Results:
The microPET images showed higher uptake of (64)Cu-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 (64)Cu-labeled FIB504.64, 6.49 +/- 2.25; control mice with (64)Cu-labeled FIB504.64, 3.64 +/- 1.12; colitis mice, (64)Cu-labeled nonspecific antibody 3.97 +/- 0.48%ID/g (P < 0.05 between groups).
Conclusions:
The selective uptake of (64)Cu-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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