Imaging of experimental colitis with a radiolabeled leukotriene B4 antagonist.
The use of radiolabeled leukocytes is considered the gold standard for scintigraphic imaging of inflammatory bowel disease. The disadvantages of (99m)Tc-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 B(4) (LTB(4)) receptors expressed on neutrophils. Imaging characteristics of the (111)In-labeled LTB(4) antagonist (DPC11870) were compared with those of (18)F-FDG and (99m)Tc-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 (99m)Tc-granulocytes, (18)F-FDG, or (111)In-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 (99m)Tc-granulocytes, both (111)In-DPC11870 and (18)F-FDG were superior in revealing the inflamed lesions. The biodistribution data showed that uptake of (111)In-DPC11870 in the inflamed colon was highest (0.72 +/- 0.18 percentage injected dose per gram [%ID/g]), followed by uptake of (99m)Tc-granulocytes (0.40 +/- 0.11 %ID/g) and of (18)F-FDG (0.16 +/- 0.04 %ID/g). Because of low activity concentrations in the noninflamed colon, the radiolabeled LTB(4) antagonist also revealed the highest ratio of affected colon to unaffected colon (11.6 for (111)In-DPC11870, 5.5 for (99m)Tc-granulocytes, and 4.1 for (18)F-FDG).


CONCLUSIONS
The radiolabeled LTB(4) 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 (111)In-DPC11870 were better than those acquired with (99m)Tc-granulocytes or (18)F-FDG.
van Eerd
Julliëtte E M
JE
Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands. J.vaneerd@nucmed.umcn.nl
Laverman
Peter
P
Oyen
Wim J G
WJ
Harris
Thomas D
TD
Edwards
D Scott
DS
Ellars
Charles E
CE
Corstens
Frans H M
FH
Boerman
Otto C
OC
D000818:Animals; D001713:Biphenyl Compounds / Q000493:pharmacokinetics*; D003092:Colitis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006098:Granulocytes / Q000000981:diagnostic imaging / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009504:Neutrophils / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009842:Oligopeptides / Q000493:pharmacokinetics*; D009928:Organ Specificity; D011725:Pyridines / Q000493:pharmacokinetics*; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019690:Technetium Tc 99m Exametazime / Q000493:pharmacokinetics; D013777:Tetrazoles / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014915:Whole-Body Counting
D001713:Biphenyl Compounds; C476701:DPC11870-11; D009842:Oligopeptides; D011725:Pyridines; D019275:Radiopharmaceuticals; D013777:Tetrazoles; D019788:Fluorodeoxyglucose F18; D007975:Leukotriene B4; D019690:Technetium Tc 99m Exametazime