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Imaging of Experimental Colitis with a Radiolabeled Leukotriene B₄ Antagonist

¹ Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands
² Discovery Research, Bristol-Myers Squibb Medical Imaging, North Billerica, Massachusetts

The use of radiolabeled leukocytes is considered the gold standard for scintigraphic imaging of inflammatory bowel disease. The disadvantages of ^99mTc-hexamethylpropyleneamine oxime (HMPAO)-leukocytes, however, encourage the search for new imaging agents with at least similar diagnostic accuracy but without the laborious preparation and subsequent risk of contamination. In this study we investigated the imaging characteristics of a new imaging agent that specifically binds to the leukotriene B₄ (LTB₄) receptors expressed on neutrophils. Imaging characteristics of the ¹¹¹In-labeled LTB₄ antagonist (DPC11870) were compared with those of ¹⁸F-FDG and ^99mTc-HMPAO-granulocytes in a rabbit model of experimental colitis. Methods: Acute colitis was induced in New Zealand White (NZW) rabbits by infusion of trinitrobenzene sulfonic acid in the descending colon. Forty-eight hours after induction of colitis, all animals were injected intravenously with ^99mTc-granulocytes, ¹⁸F-FDG, or ¹¹¹In-DPC11870. The pharmacokinetics and biodistribution were studied by serial scintigraphic imaging and by ex vivo counting of dissected tissues. Results: All 3 radiopharmaceuticals showed the inflamed colon as early as 1 h after injection. However, compared with ^99mTc-granulocytes, both ¹¹¹In-DPC11870 and ¹⁸F-FDG were superior in revealing the inflamed lesions. The biodistribution data showed that uptake of ¹¹¹In-DPC11870 in the inflamed colon was highest (0.72 ± 0.18 percentage injected dose per gram [%ID/g]), followed by uptake of ^99mTc-granulocytes (0.40 ± 0.11 %ID/g) and of ¹⁸F-FDG (0.16 ± 0.04 %ID/g). Because of low activity concentrations in the noninflamed colon, the radiolabeled LTB₄ antagonist also revealed the highest ratio of affected colon to unaffected colon (11.6 for ¹¹¹In-DPC11870, 5.5 for ^99mTc-granulocytes, and 4.1 for ¹⁸F-FDG). Conclusion: The radiolabeled LTB₄ antagonist DPC11870 clearly delineated acute colitis lesions in NZW rabbits within 1 h after injection. Because of high uptake in the inflamed lesions and a low activity concentration in the noninflamed colon, images acquired with ¹¹¹In-DPC11870 were better than those acquired with ^99mTc-granulocytes or ¹⁸F-FDG.

Key Words: LTB₄ antagonist • infection imaging • inflammatory bowel disease • granulocytes • ¹⁸F-FDG

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