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Scintigraphic Detection of Pulmonary Aspergillosis in Rabbits with a Radiolabeled Leukotriene B4 Antagonist

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

Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we decided to test the imaging characteristics of this agent in a more clinically relevant model of pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the ¹¹¹In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits with experimental pulmonary aspergillosis infection. The imaging characteristics of ¹¹¹In-DPC11870 were compared with those of ⁶⁷Ga-citrate, a radiopharmaceutical commonly used to detect pulmonary infections in patients. Methods: Pulmonary aspergillosis was induced in the left lung of rabbits by intratracheal inoculation of 1 x 10⁸ conidia of Aspergillus fumigatus. Three days after the inoculation, the rabbits received ¹¹¹In-DPC11870 or ⁶⁷Ga-citrate intravenously. Images were acquired at several time points up to 24 h after injection. Results: Pulmonary aspergillosis was visualized with both agents. Images acquired after injection of ¹¹¹In-DPC11870 showed uptake in the pulmonary lesions from 6 h after injection. Because of accumulation at the site of infection and clearance from the background, the images improved with time. Region-of-interest analysis at 24 h after injection revealed infected lung–to–normal lung ratios of 5.0 ± 1.5 for ¹¹¹In-DPC11870 and 2.9 ± 0.6 for ⁶⁷Ga-citrate. Conclusion: The radiolabeled LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary aspergillosis in rabbits. Images acquired at 24 h after injection of ¹¹¹In-DPC11870 were superior to those obtained after injection of ⁶⁷Ga-citrate.

Key Words: LTB4 antagonist • aspergillosis • scintigraphy • ⁶⁷Ga-citrate

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