Detection of intestinal inflammation by MicroPET imaging using a (64)Cu-labeled anti-beta(7) integrin antibody.
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.
Dearling
Jason L J
JL
Division of Nuclear Medicine, Department of Radiology, Children's Hospital, Boston, Massachusetts 02115, USA. jason.dearling@childrens.harvard.edu
Park
Eun Jeong
EJ
Dunning
Patricia
P
Baker
Amanda
A
Fahey
Frederic
F
Treves
S Ted
ST
Soriano
Sulpicio G
SG
Shimaoka
Motomu
M
Packard
Alan B
AB
Peer
Dan
D
D000818:Animals; D000911:Antibodies, Monoclonal; D003092:Colitis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000276:immunology; D003301:Copper Radioisotopes; D016264:Dextran Sulfate / Q000633:toxicity; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000276:immunology; D039641:Integrin beta Chains / Q000276:immunology*; D007413:Intestinal Mucosa / Q000000981:diagnostic imaging*; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D016719:Radioimmunodetection; D019275:Radiopharmaceuticals; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; D039641:Integrin beta Chains; D019275:Radiopharmaceuticals; C091368:integrin beta7; D016264:Dextran Sulfate