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Specific and Rapid Scintigraphic Detection of Infection with ^99mTc-Labeled Interleukin-8

Departments of Nuclear Medicine and Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands

Interleukin-8 (IL-8) is a chemotactic cytokine involved in activation and recruitment of neutrophils to areas of infection. In our previous studies in rabbits we tested ¹²³I-labeled IL-8 for its potential to image infections and showed that IL-8 rapidly and efficiently accumulated in infectious foci. However, labeling of IL-8 with ¹²³I is costly and laborious and the specific activity of the preparation was low. In this study IL-8 was labeled with ^99mTc through the hydrazinonicotinamide (HYNIC) chelator. Methods: The leukocyte receptor-binding capacity of the preparation was determined in vitro. Rabbits with Escherichia coli abscesses were injected intravenously with 7 MBq ^99mTc-HYNIC-IL-8. Biodistribution of the radiolabel was determined by gamma camera imaging and tissue counting at 8 h after injection. ^99mTc-HYNIC-lysozyme was used as a size-matched control. Results: The leukocyte receptor-binding capacity of the ^99mTc-HYNIC-IL-8 preparation was preserved as determined in vitro, but labeling efficiency was modest with a specific activity of 3 MBq/µg. ^99mTc-HYNIC-IL-8 accumulated rapidly in the abscess up to 0.33 ± 0.06 percentage injected dose per gram (%ID/g) at 8 h after injection (vs. 0.025 ± 0.003 %ID/g for ^99mTc-HYNIC-lysozyme). Total uptake in the abscess was 4.9 ± 0.7 %ID (vs. 0.44 ± 0.05 %ID for ^99mTc-HYNIC-lysozyme). Abscess-to-contralateral muscle ratios increased up to 127 ± 23 (compared with 6.7 ± 1.1 for ^99mTc-HYNIC-lysozyme) and abscess-to-blood ratios increased to 11.9 ± 2.2 (0.24 ± 0.03 for ^99mTc-HYNIC-lysozyme). The radiolabel was excreted renally, with a retention in the kidneys of 28 %ID. Gamma camera imaging rapidly visualized the abscess from 1 h after injection onward, with abscess-to-background ratios improving with time up to 22 at 8 h after injection (vs. 2.7 for ^99mTc-HYNIC-lysozyme), as determined by quantitative analysis of the images. Most important, only a transient (30 min) moderate drop of leukocyte counts and no leukocytosis were observed after injection of an imaging dose of ^99mTc-HYNIC-IL-8. Conclusion: IL-8 can be labeled with ^99mTc using HYNIC as a chelator. By this method the leukocyte receptor-binding capacity is preserved. The preparation allows rapid visualization of infection in a rabbit model with high target-to-background ratios. The mild transient drop of leukocyte counts and the absence of leukocytosis suggest that ^99mTc-HYNIC-IL-8 may be used as an imaging agent with only mild and transient side effects.

Key Words: interleukin-8 • infection • scintigraphic imaging • biodistribution • ^99mTc

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