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Dedicated Pinhole SPECT of Intestinal Neutrophil Recruitment in a Mouse Model of Dextran Sulfate Sodium–Induced Colitis

¹ Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
² Department of Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands
³ Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
⁴ Department of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

Evaluating the efficacy of therapy in experimental inflammatory bowel disease (IBD) requires information about inflammatory activity in bowel segments or leukocyte recruitment and about kinetics in the follow-up of treatment. This study evaluated a noninvasive scintigraphic technique able to assess neutrophil trafficking in a mouse model of dextran sulfate sodium (DSS)–induced colitis. Methods: Groups of 4 BALB/c mice were assessed at baseline and after 1, 3, 5, and 8 d of treatment with DSS. Donor neutrophils were harvested by rinsing of the peritoneal cavity with phosphate-buffered saline 5 h after intraperitoneal injection of proteose peptone contained in phosphate-buffered saline and labeled with freshly prepared ^99mTc-hexamethylpropylene amine oxime (HMPAO). Pinhole SPECT of the abdomen was performed 1 h after reinjection of 50 MBq of labeled neutrophils. In addition, the severity of inflammation was determined by histologic examination. The possibilities of the technique were illustrated by scintigraphic assessment of neutrophil trafficking with and without blocking of neutrophil migration by a CD97 monoclonal antibody in mice with DSS-induced colitis. Results: Colonic uptake of ^99mTc-HMPAO neutrophils was determined with dedicated animal pinhole SPECT in mice with DSS-induced colitis and correlated well with histologic findings (R = 0.81) and wet colon weight (R = 0.87) and moderately with clinical weight loss (R = 0.62). The neutrophil uptake ratio was reduced significantly (P < 0.01) by blocking of neutrophil migration capacity with the CD97 antibody. Conclusion: Animal pinhole SPECT can be used to study inflammatory activity and neutrophil recruitment in vivo in experimental colitis.

Key Words: ^99mTc-HMPAO • pinhole SPECT • neutrophils • inflammatory bowel disease • dextran sulfate sodium colitis

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