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Journal of Nuclear Medicine Vol. 46 No. 9 1546-1551
© 2005 by Society of Nuclear Medicine

Basic Science Investigations

Imaging of Infection and Inflammation with an Improved 99mTc-Labeled LTB4 Antagonist

Julliëtte E.M. van Eerd, MSc1, Matthias Broekema, MSc2, Thomas D. Harris, PhD3, D. Scott Edwards, PhD3, Wim J.G. Oyen, MD1, Frans H.M. Corstens, MD1 and Otto C. Boerman, PhD1

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

Studies have demonstrated that the bivalent 111In-labeled leukotriene B4 (LTB4) antagonist DPC11870reveals infectious and inflammatory lesions in various rabbit models. The radioactive tracer accumulates quickly at the site of infection and clears rapidly from the circulation, resulting in high-quality images. In this study, 2 new hydrazinonicotinamide (HYNIC)-conjugated compounds that are structurally related to DPC11870were studied to further improve image quality. Methods: A bivalent HYNIC-conjugated LTB4 antagonist (MB81) and a monovalent one (MB88) were labeled with 99mTc. The radiolabeled compounds were intravenously injected into New Zealand White rabbits with E. coli infection in the left thigh muscle. The imaging characteristics of both compounds were compared with those of the bivalent 111In-labeled LTB4 antagonist. Results: Both 99mTc-labeled LTB4 antagonists revealed the abscess from 2 h after injection onward. Abscess uptake at 8 h after injection was similar for both compounds (0.22 ± 0.08 percentage injected dose per gram [%ID/g] and 0.36 ± 0.13 %ID/g for the bivalent and monovalent compounds, respectively). However, visualization of the abscess and the quality of the images were better after injection of MB88 than after injection of either of the bivalent LTB4 antagonists. The excellent delineation of the abscess by MB88 was mainly due to the more rapid clearance of this compound from nontarget organs. Conclusion: The 99mTc-labeled HYNIC conjugated LTB4 antagonists MB88 and MB81 revealed infectious foci in rabbits within a few hours after injection. Imaging characteristics of monovalent 99mTc-MB88 were superior to those of the bivalent LTB4 antagonists DPC11870and MB81. Therefore, of the 3 LTB4 antagonists, the monovalent LTB4 antagonist MB88 is the most potent and promising agent for visualizing and evaluating infection and inflammation in patients.

Key Words: LTB4 antagonist • infection imaging • scintigraphy


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