Imaging of intestinal lymphocyte homing by means of pinhole SPECT in a TNBS colitis mouse model.
OBJECTIVE
The increasing knowledge of the molecular basis of leukocyte trafficking results in the development of novel anti-inflammatory strategies for inflammatory bowel disease (IBD). For optimal evaluation of therapy efficacy, information about inflammatory activity in bowel segments or lymphocyte recirculation and kinetics in the follow-up of experimental treatment for IBD is needed. The aim of this study was to evaluate a non-invasive scintigraphic technique, able to assess lymphocyte trafficking in a trinitrobenzene sulfonic acid (TNBS) induced mouse colitis model of IBD.


METHODS
TNBS sensitized and non-sensitized murine total splenocytes were labeled in vitro with 111In-oxine and injected into either control or TNBS colitis BALB/c mice. Biodistribution and specific radioactive uptake, representing transferred cells, were determined by serial dedicated animal planar scintigraphy and pinhole SPECT of the abdomen 4, 24 and 48h post injection of labeled cells. In addition, the severity of inflammation was determined by histological scoring.


RESULTS
Migration of 111In labeled splenocytes to the colon increased in time and was maximal at 48h after administration. The highest specific radioactive uptake ratio in the colon after 48h was observed in mice with TNBS colitis that received TNBS sensitized lymphocytes. Histological scoring confirmed the presence of colitis in the TNBS treated groups.


CONCLUSIONS
Homing of TNBS-sensitized lymphocytes can be assessed in vivo by means of dedicated animal pinhole SPECT. Generally, this technique enables serial measurement of specific cell trafficking with potential of in vivo evaluation of novel anti-inflammatory strategies in inflammatory bowel disease.
Bennink
Roelof J
RJ
Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands. r.bennink@amc.uva.nl
van Montfrans
Catherine
C
de Jonge
Wouter J
WJ
de Bruin
Kora
K
van Deventer
Sander J
SJ
te Velde
Anje A
AA
D000818:Animals; D002465:Cell Movement; D003092:Colitis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003106:Colon / Q000000981:diagnostic imaging / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism; D008214:Lymphocytes / Q000000981:diagnostic imaging*; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D015125:Oxyquinoline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000295:instrumentation* / Q000379:methods; D014302:Trinitrobenzenesulfonic Acid
D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D016201:Receptors, Lymphocyte Homing; C032950:indium oxine; D015125:Oxyquinoline; D014302:Trinitrobenzenesulfonic Acid